About this Journal Submit a Manuscript Table of Contents
Clinical and Developmental Immunology
Volume 2012 (2012), Article ID 153863, 14 pages
http://dx.doi.org/10.1155/2012/153863
Review Article

Functional Avidity: A Measure to Predict the Efficacy of Effector T Cells?

1Divisions of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland
2Swiss Vaccine Research Institute, 1011 Lausanne, Switzerland

Received 21 August 2012; Accepted 22 October 2012

Academic Editor: Graham Ogg

Copyright © 2012 Selena Viganò et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. N. Zhang and M. Bevan, “CD8+ T cells: foot soldiers of the immune system,” Immunity, vol. 35, no. 2, pp. 161–168, 2011. View at Publisher · View at Google Scholar · View at Scopus
  2. R. A. Koup, J. T. Safrit, Y. Cao et al., “Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome,” Journal of Virology, vol. 68, no. 7, pp. 4650–4655, 1994. View at Scopus
  3. P. Borrow, H. Lewicki, B. H. Hahn, G. M. Shaw, and M. B. A. Oldstone, “Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection,” Journal of Virology, vol. 68, no. 9, pp. 6103–6110, 1994. View at Scopus
  4. X. Jin, D. E. Bauer, S. E. Tuttleton et al., “Dramatic rise in plasma viremia after CD8+ T cell depletion in simian immunodeficiency virus-infected macaques,” Journal of Experimental Medicine, vol. 189, no. 6, pp. 991–998, 1999. View at Publisher · View at Google Scholar · View at Scopus
  5. J. E. Schmitz, M. J. Kuroda, S. Santra et al., “Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes,” Science, vol. 283, no. 5403, pp. 857–860, 1999. View at Publisher · View at Google Scholar · View at Scopus
  6. C. B. Moore, M. John, I. R. James, F. T. Christiansen, C. S. Witt, and S. A. Mallal, “Evidence of HIV-1 adaptation to HLA-restricted immune responses at a population level,” Science, vol. 296, no. 5572, pp. 1439–1443, 2002. View at Publisher · View at Google Scholar · View at Scopus
  7. F. Pereyra, M. M. Addo, D. E. Kaufmann et al., “Genetic and immunologic heterogeneity among persons who control HIV infection in the absence of therapy,” Journal of Infectious Diseases, vol. 197, no. 4, pp. 563–571, 2008. View at Publisher · View at Google Scholar · View at Scopus
  8. A. R. Hersperger, F. Pereyra, M. Nason et al., “Perforin expression directly ex vivo by HIV-specific CD8 T-cells is a correlate of HIV elite control,” PLoS pathogens, vol. 6, no. 5, Article ID e1000917, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. A. Harari, S. C. Zimmerli, and G. Pantaleo, “Cytomegalovirus (CMV)-specific cellular immune responses,” Human Immunology, vol. 65, no. 5, pp. 500–506, 2004. View at Publisher · View at Google Scholar · View at Scopus
  10. A. Harari, V. Dutoit, C. Cellerai, P. A. Bart, R. A. Du Pasquier, and G. Pantaleo, “Functional signatures of protective antiviral T-cell immunity in human virus infections,” Immunological Reviews, vol. 211, pp. 236–254, 2006. View at Publisher · View at Google Scholar · View at Scopus
  11. E. J. Wherry, J. N. Blattman, K. Murali-Krishna, R. Van Der Most, and R. Ahmed, “Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment,” Journal of Virology, vol. 77, no. 8, pp. 4911–4927, 2003. View at Publisher · View at Google Scholar · View at Scopus
  12. A. R. Hersperger, J. N. Martin, L. Y. Shin et al., “Increased HIV-specific CD8+ T-cell cytotoxic potential in HIV elite controllers is associated with T-bet expression,” Blood, vol. 117, no. 14, pp. 3799–3808, 2011. View at Publisher · View at Google Scholar · View at Scopus
  13. S. Reichstetter, W. W. Kwok, S. Kochik, D. M. Koelle, J. S. Beaty, and G. T. Nepom, “MHC-peptide ligand interactions establish a functional threshold for antigen-specific T cell recognition,” Human Immunology, vol. 60, no. 7, pp. 608–618, 1999. View at Publisher · View at Google Scholar · View at Scopus
  14. I. Messaoudi, J. A. Guevara Patiño, R. Dyall, J. LeMaoult, and J. Nikolich-Žugich, “Direct link between mhc polymorphism, T cell avidity, and diversity in immune defense,” Science, vol. 298, no. 5599, pp. 1797–1800, 2002. View at Publisher · View at Google Scholar · View at Scopus
  15. F. Pereyra, X. Jia, P. J. McLaren, A. Telenti, P. I. W. De Bakker, and B. D. Walker, “The major genetic determinants of HIV-1 control affect HLA class I peptide presentation,” Science, vol. 330, no. 6010, pp. 1551–1557, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. P. Klepiela, A. J. Leslie, I. Honeyborne et al., “Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA,” Nature, vol. 432, no. 7018, pp. 769–774, 2004. View at Publisher · View at Google Scholar · View at Scopus
  17. D. R. Chopera, M. Mlotshwa, Z. Woodman et al., “Virological and immunological factors associated with HIV-1 differential disease progression in HLA-B*58:01-positive individuals,” Journal of Virology, vol. 85, no. 14, pp. 7070–7080, 2011. View at Publisher · View at Google Scholar · View at Scopus
  18. Y. Peretz, O. Marra, R. Thomas et al., “Relative contribution of HIV-specific functional lymphocyte subsets restricted by protective and non-protective HLA alleles,” Viral Immunology, vol. 24, no. 3, pp. 189–198, 2011. View at Publisher · View at Google Scholar · View at Scopus
  19. R. P. Payne, H. Kløverpris, J. B. Sacha et al., “Efficacious early antiviral activity of HIV Gag- and Pol-specific HLA-B*2705-restricted CD8+ T cells,” Journal of Virology, vol. 84, no. 20, pp. 10543–10557, 2010. View at Publisher · View at Google Scholar · View at Scopus
  20. S. A. Migueles, M. S. Sabbaghian, W. L. Shupert et al., “HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 6, pp. 2709–2714, 2000. View at Publisher · View at Google Scholar · View at Scopus
  21. M. Carrington and S. J. O'Brien, “The Influence of HLA Genotype on AIDS,” Annual Review of Medicine, vol. 54, pp. 535–551, 2003. View at Publisher · View at Google Scholar · View at Scopus
  22. M. P. Martin, X. Gao, J. H. Lee et al., “Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS,” Nature Genetics, vol. 31, no. 4, pp. 429–434, 2002. View at Publisher · View at Google Scholar · View at Scopus
  23. M. Ahmadzadeh, L. A. Johnson, B. Heemskerk et al., “Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired,” Blood, vol. 114, no. 8, pp. 1537–1544, 2009. View at Publisher · View at Google Scholar · View at Scopus
  24. C. L. Day, D. E. Kaufmann, P. Kiepiela et al., “PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression,” Nature, vol. 443, no. 7109, pp. 350–354, 2006. View at Publisher · View at Google Scholar · View at Scopus
  25. S. Urbani, B. Amadei, D. Tola et al., “PD-1 expression in acute hepatitis C virus (HCV) infection is associated with HCV-specific CD8 exhaustion,” Journal of Virology, vol. 80, no. 22, pp. 11398–11403, 2006. View at Publisher · View at Google Scholar · View at Scopus
  26. D. H. O'Connor, T. M. Allen, T. U. Vogel et al., “Acute phase cytotoxic T lymphocyte escape is a hallmark of simian immunodeficiency virus infection,” Nature Medicine, vol. 8, no. 5, pp. 493–499, 2002. View at Publisher · View at Google Scholar · View at Scopus
  27. C. L. Pérez, K. Hasselrot, G. Bratt, K. Broliden, and A. C. Karlsson, “Induction of systemic HIV-1-specific cellular immune responses by oral exposure in the uninfected partner of discordant couples,” AIDS, vol. 24, no. 7, pp. 969–974, 2010. View at Publisher · View at Google Scholar · View at Scopus
  28. K. Hasselrot, “Genital and oral mucosal immune response against HIV-1 in exposed uninfected individuals,” Critical Reviews in Immunology, vol. 29, no. 5, pp. 369–377, 2009. View at Scopus
  29. K. Hasselrot, G. Bratt, T. Hirbod et al., “Orally exposed uninfected individuals have systemic anti-HIV responses associating with partners' viral load,” AIDS, vol. 24, no. 1, pp. 35–43, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. A. L. Erickson, C. B. Willberg, V. McMahan et al., “Potentially exposed but uninfected individuals produce cytotoxic and polyfunctional human immunodeficiency virus type 1-specific CD8+ T-cell responses which can be defined to the epitope level,” Clinical and Vaccine Immunology, vol. 15, no. 11, pp. 1745–1748, 2008. View at Publisher · View at Google Scholar · View at Scopus
  31. M. R. Betts and A. Harari, “Phenotype and function of protective T cell immune responses in HIV,” Current Opinion in HIV and AIDS, vol. 3, no. 3, pp. 349–355, 2008. View at Publisher · View at Google Scholar · View at Scopus
  32. F. Pereyra, X. Jia, P. J. McLaren, A. Telenti, P. I. W. De Bakker, and B. D. Walker, “The major genetic determinants of HIV-1 control affect HLA class I peptide presentation,” Science, vol. 330, no. 6010, pp. 1551–1557, 2010. View at Publisher · View at Google Scholar · View at Scopus
  33. J. Fellay, K. V. Shianna, D. Ge et al., “A whole-genome association study of major determinants for host control of HIV-1,” Science, vol. 317, no. 5840, pp. 944–947, 2007. View at Publisher · View at Google Scholar · View at Scopus
  34. A. Porgador, J. W. Yewdell, Y. Deng, J. R. Bennink, and R. N. Germain, “Localization, quantitation, and in situ detection of specific peptide- MHC class I complexes using a monoclonal antibody,” Immunity, vol. 6, no. 6, pp. 715–726, 1997. View at Publisher · View at Google Scholar · View at Scopus
  35. M. R. Betts, D. A. Price, J. M. Brenchley et al., “The functional profile of primary human antiviral CD8+ T cell effector activity is dictated by cognate peptide concentration,” Journal of Immunology, vol. 172, no. 10, pp. 6407–6417, 2004. View at Scopus
  36. A. Harari, C. Cellerai, F. B. Enders et al., “Skewed association of polyfunctional antigen-specific CD8 T cell populations with HLA-B genotype,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 41, pp. 16233–16238, 2007. View at Publisher · View at Google Scholar · View at Scopus
  37. A. Langenkamp, G. Casorati, C. Garavaglia, P. Dellabona, A. Lanzavecchia, and F. Sallusto, “T cell priming by dendritic cells: thresholds for proliferation, differentiation and death and intraclonal functional diversification,” European Journal of Immunology, vol. 32, no. 7, pp. 2046–2054, 2002. View at Publisher · View at Google Scholar · View at Scopus
  38. W. W. A. Schamel, I. Arechaga, R. M. Risueño et al., “Coexistence of multivalent and monovalent TCRs explains high sensitivity and wide range of response,” Journal of Experimental Medicine, vol. 202, no. 4, pp. 493–503, 2005. View at Publisher · View at Google Scholar · View at Scopus
  39. A. G. Cawthon, H. Lu, and M. A. Alexander-Miller, “Peptide requirement for CTL activation reflects the sensitivity to CD3 engagement: correlation with CD8αβ versus CD8αα expression,” Journal of Immunology, vol. 167, no. 5, pp. 2577–2584, 2001. View at Scopus
  40. A. Viola and A. Lanzavecchia, “T cell activation determined by T cell receptor number and tunable thresholds,” Science, vol. 273, no. 5271, pp. 104–106, 1996. View at Scopus
  41. S. Valitutti, S. Müller, M. Dessing, and A. Lanzavecchia, “Different responses are elicited in cytotoxic T lymphocytes by different levels of T cell receptor occupancy,” Journal of Experimental Medicine, vol. 183, no. 4, pp. 1917–1921, 1996. View at Publisher · View at Google Scholar · View at Scopus
  42. J. D. Stone, A. S. Chervin, and D. M. Kranz, “T-cell receptor binding affinities and kinetics: impact on T-cell activity and specificity,” Immunology, vol. 126, no. 2, pp. 165–176, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. D. Zehn, C. King, M. J. Bevan, and E. Palmer, “TCR signaling requirements for activating T cells and for generating memory,” Cellular and Molecular Life Sciences, vol. 69, no. 10, pp. 1565–1575, 2012. View at Publisher · View at Google Scholar · View at Scopus
  44. S. M. Alam, P. J. Travers, J. L. Wung et al., “T cell-receptor affinity and thymocyte positive selection,” Nature, vol. 381, no. 6583, pp. 616–620, 1996. View at Publisher · View at Google Scholar · View at Scopus
  45. P. D. Holler, A. R. Lim, B. K. Cho, L. A. Rund, and D. M. Kranz, “CD8-T cell transfectants that express a high affinity T cell receptor exhibit enhanced peptide-dependent activation,” Journal of Experimental Medicine, vol. 194, no. 8, pp. 1043–1052, 2001. View at Publisher · View at Google Scholar · View at Scopus
  46. S. Tian, R. Maile, E. J. Collins, and J. A. Frelinger, “CD8+ T cell activation is governed by TCR-peptide/MHC affinity, not dissociation rate,” Journal of Immunology, vol. 179, no. 5, pp. 2952–2960, 2007. View at Scopus
  47. K. Matsui, J. J. Boniface, P. Steffner, P. A. Reay, and M. M. Davis, “Kinetics of T-cell receptor binding to peptide/I-E(k) complexes: correlation of the dissociation rate with T-cell responsiveness,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 26, pp. 12862–12866, 1994. View at Publisher · View at Google Scholar · View at Scopus
  48. N. L. La Gruta, P. C. Doherty, and S. J. Turner, “A correlation between function and selected measures of T cell avidity in influenza virus-specific CD8+ T cell responses,” European Journal of Immunology, vol. 36, no. 11, pp. 2951–2959, 2006. View at Publisher · View at Google Scholar · View at Scopus
  49. T. W. Mckeithan, “Kinetic proofreading in T-cell receptor signal transduction,” Proceedings of the National Academy of Sciences of the United States of America, vol. 92, no. 11, pp. 5042–5046, 1995. View at Publisher · View at Google Scholar · View at Scopus
  50. J. Huang, V. I. Zarnitsyna, B. Liu et al., “The kinetics of two-dimensional TCR and pMHC interactions determine T-cell responsiveness,” Nature, vol. 464, no. 7290, pp. 932–936, 2010. View at Publisher · View at Google Scholar · View at Scopus
  51. K. Holmberg, S. Mariathasan, T. Ohteki, P. S. Ohashi, and N. R. J. Gascoigne, “TCR binding kinetics measured with MHC class I tetramers reveal a positive selecting peptide with relatively high affinity for TCR,” Journal of Immunology, vol. 171, no. 5, pp. 2427–2434, 2003. View at Scopus
  52. C. Yee, P. A. Savage, P. P. Lee, M. M. Davis, and P. D. Greenberg, “Isolation of high avidity melanoma-reactive CTL from heterogeneous populations using peptide-MHC tetramers,” Journal of Immunology, vol. 162, no. 4, pp. 2227–2234, 1999. View at Scopus
  53. D. Naeher, M. A. Daniels, B. Hausmann, P. Guillaume, I. Luescher, and E. Palmer, “A constant affinity threshold for T cell tolerance,” Journal of Experimental Medicine, vol. 204, no. 11, pp. 2553–2559, 2007. View at Publisher · View at Google Scholar · View at Scopus
  54. N. Labrecque, L. S. Whitfield, R. Obst, C. Waltzinger, C. Benoist, and D. Mathis, “How much TCR does a T cell need?” Immunity, vol. 15, no. 1, pp. 71–82, 2001. View at Publisher · View at Google Scholar · View at Scopus
  55. M. Hofmann, M. Radsak, G. Rechtsteiner et al., “T cell avidity determines the level of CTL activation,” European Journal of Immunology, vol. 34, no. 7, pp. 1798–1806, 2004. View at Publisher · View at Google Scholar · View at Scopus
  56. R. König, “Interactions between MHC molecules and co-receptors of the TCR,” Current Opinion in Immunology, vol. 14, no. 1, pp. 75–83, 2002. View at Publisher · View at Google Scholar · View at Scopus
  57. E. M. L. Choi, J. L. Chen, L. Wooldridge et al., “High avidity antigen-specific CTL identified by CD8-independent tetramer staining,” Journal of Immunology, vol. 171, no. 10, pp. 5116–5123, 2003. View at Scopus
  58. P. D. Holler and D. M. Kranz, “Quantitative analysis of the contribution of TCR/pepMHC affinity and CD8 to T cell activation,” Immunity, vol. 18, no. 2, pp. 255–264, 2003. View at Publisher · View at Google Scholar · View at Scopus
  59. N. Khan, M. Cobbold, J. Cummerson, and P. A. H. Moss, “Persistent viral infection in humans can drive high frequency low-affinity T-cell expansions,” Immunology, vol. 131, no. 4, pp. 537–548, 2010. View at Publisher · View at Google Scholar · View at Scopus
  60. B. Laugel, H. A. Van Den Berg, E. Gostick et al., “Different T cell receptor affinity thresholds and CD8 coreceptor dependence govern cytotoxic T lymphocyte activation and tetramer binding properties,” Journal of Biological Chemistry, vol. 282, no. 33, pp. 23799–23810, 2007. View at Publisher · View at Google Scholar · View at Scopus
  61. M. A. Daniels and S. C. Jameson, “Critical role for CD8 in T cell receptor binding and activation by peptide/major histocompatibility complex multimers,” Journal of Experimental Medicine, vol. 191, no. 2, pp. 335–346, 2000. View at Publisher · View at Google Scholar · View at Scopus
  62. H. Xu and D. R. Littman, “A kinase-independent function of Lck in potentiating antigen-specific T cell activation,” Cell, vol. 74, no. 4, pp. 633–643, 1993. View at Publisher · View at Google Scholar · View at Scopus
  63. M. Thome, V. Germain, J. P. DiSanto, and O. Acuto, “The p56(lck) SH2 domain mediates recruitment of CD8/p56(lck) to the activated T cell receptor/CD3/ξ complex,” European Journal of Immunology, vol. 26, no. 9, pp. 2093–2100, 1996. View at Scopus
  64. H. Y. Irie, K. S. Ravichandran, and S. J. Burakoff, “CD8β chain influences CD8α chain-associated Lck kinase activity,” Journal of Experimental Medicine, vol. 181, no. 4, pp. 1267–1273, 1995. View at Publisher · View at Google Scholar · View at Scopus
  65. Z. Xiao, M. F. Mescher, and S. C. Jameson, “Detuning CD8 T cells: down-regulation of CD8 expression, tetramer binding, and response during CTL activation,” Journal of Experimental Medicine, vol. 204, no. 11, pp. 2667–2677, 2007. View at Publisher · View at Google Scholar · View at Scopus
  66. E. Gostick, D. K. Cole, S. L. Hutchinson et al., “Functional and biophysical characterization of an HLA-A* 6801-restricted HIV-specific T cell receptor,” European Journal of Immunology, vol. 37, no. 2, pp. 479–486, 2007. View at Publisher · View at Google Scholar · View at Scopus
  67. L. Wooldridge, A. Lissina, J. Vernazza et al., “Enhanced immunogenicity of CTL antigens through mutation of the CD8 binding MHC class I invariant region,” European Journal of Immunology, vol. 37, no. 5, pp. 1323–1333, 2007. View at Publisher · View at Google Scholar · View at Scopus
  68. G. Schonrich, U. Kalinke, F. Momburg et al., “Down-regulation of T cell receptors on self-reactive T cells as a novel mechanism for extrathymic tolerance induction,” Cell, vol. 65, no. 2, pp. 293–304, 1991. View at Publisher · View at Google Scholar · View at Scopus
  69. O. Acuto, V. D. Bartolo, and F. Michel, “Tailoring T-cell receptor signals by proximal negative feedback mechanisms,” Nature Reviews Immunology, vol. 8, no. 9, pp. 699–712, 2008. View at Publisher · View at Google Scholar · View at Scopus
  70. M. A. Daniels, E. Teixeiro, J. Gill et al., “Thymic selection threshold defined by compartmentalization of Ras/MAPK signalling,” Nature, vol. 444, no. 7120, pp. 724–729, 2006. View at Publisher · View at Google Scholar · View at Scopus
  71. R. M. Luik and R. S. Lewis, “New insights into the molecular mechanisms of store-operated Ca2+ signaling in T cells,” Trends in Molecular Medicine, vol. 13, no. 3, pp. 103–107, 2007. View at Publisher · View at Google Scholar · View at Scopus
  72. S. M. Anderton and D. C. Wraith, “Selection and fine-tuning of the autoimmune T-cell repertoire,” Nature Reviews Immunology, vol. 2, no. 7, pp. 487–498, 2002. View at Scopus
  73. P. J. Ebert, S. Jiang, J. Xie, Q. J. Li, and M. M. Davis, “An endogenous positively selecting peptide enhances mature T cell responses and becomes an autoantigen in the absence of microRNA miR-181a,” Nature immunology, vol. 10, no. 11, pp. 1162–1169, 2009. View at Publisher · View at Google Scholar · View at Scopus
  74. Z. Garcia, E. Pradelli, S. Celli, H. Beuneu, A. Simon, and P. Bousso, “Competition for antigen determines the stability of T cell-dendritic cell interactions during clonal expansion,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 11, pp. 4553–4558, 2007. View at Publisher · View at Google Scholar · View at Scopus
  75. G. M. Davey, S. L. Schober, B. T. Endrizzi, A. K. Dutcher, S. C. Jameson, and K. A. Hogquist, “Preselection thymocytes are more sensitive to T cell receptor stimulation than mature T cells,” Journal of Experimental Medicine, vol. 188, no. 10, pp. 1867–1874, 1998. View at Publisher · View at Google Scholar · View at Scopus
  76. H. Pircher, U. Hoffmann Rohrer, D. Moskophidis, R. M. Zinkernagel, and H. Hengartner, “Lower receptor avidity required for thymic clonal deletion than for effector T-cell function,” Nature, vol. 351, no. 6326, pp. 482–485, 1991. View at Publisher · View at Google Scholar · View at Scopus
  77. H. S. Azzam, A. Grinberg, K. Lui, H. Shen, E. W. Shores, and P. E. Love, “CD5 expression is developmentally regulated by T cell receptor (TCR) signals and TCR avidity,” Journal of Experimental Medicine, vol. 188, no. 12, pp. 2301–2311, 1998. View at Publisher · View at Google Scholar · View at Scopus
  78. M. Bamberger, A. M. Santos, C. M. Gonçalves et al., “A new pathway of CD5 glycoprotein-mediated T cell inhibition dependent on inhibitory phosphorylation of fyn kinase,” Journal of Biological Chemistry, vol. 286, no. 35, pp. 30324–30336, 2011. View at Publisher · View at Google Scholar · View at Scopus
  79. D. Hawiger, R. F. Masilamani, E. Bettelli, V. K. Kuchroo, and M. C. Nussenzweig, “Immunological unresponsiveness characterized by increased expression of CD5 on peripheral T cells induced by dendritic cells in vivo,” Immunity, vol. 20, no. 6, pp. 695–705, 2004. View at Publisher · View at Google Scholar · View at Scopus
  80. S. K. Sharma and M. A. Alexander-Miller, “Increased sensitivity to antigen in high avidity CD8+ T cells results from augmented membrane proximal T-cell receptor signal transduction,” Immunology, vol. 133, no. 3, pp. 307–317, 2011. View at Publisher · View at Google Scholar · View at Scopus
  81. M. K. Slifka and J. L. Whitton, “Functional avidity maturation of CD8+ T cells without selection of higher affinity TCR,” Nature Immunology, vol. 2, no. 8, pp. 711–717, 2001. View at Publisher · View at Google Scholar · View at Scopus
  82. A. Bhandoola, X. Tai, M. Eckhaus et al., “Peripheral expression of self-MHC-II influences the reactivity and self-tolerance of mature CD4+ T cells: evidence from a lymphopenic T cell model,” Immunity, vol. 17, no. 4, pp. 425–436, 2002. View at Publisher · View at Google Scholar · View at Scopus
  83. I. Štefanoví, J. R. Dorfman, and R. N. Germain, “Self-recognition promotes the foreign antigen sensitivity of naive T lymphocytes,” Nature, vol. 420, no. 6914, pp. 429–434, 2002. View at Publisher · View at Google Scholar · View at Scopus
  84. I. Miconnet, A. Marrau, A. Farina et al., “Large TCR diversity of virus-specific CD8 T cells provides the mechanistic basis for massive TCR renewal after antigen exposure,” Journal of Immunology, vol. 186, no. 12, pp. 7039–7049, 2011. View at Publisher · View at Google Scholar · View at Scopus
  85. K. L. Schaubert, D. A. Price, N. Frahm et al., “Availability of a diversely avid CD8+ T cell repertoire specific for the subdominant HLA-A2-restricted HIV-1 Gag p2419-27 epitope,” Journal of Immunology, vol. 178, no. 12, pp. 7756–7766, 2007. View at Scopus
  86. J. R. Almeida, D. A. Price, L. Papagno et al., “Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover,” Journal of Experimental Medicine, vol. 204, no. 10, pp. 2473–2485, 2007. View at Publisher · View at Google Scholar · View at Scopus
  87. D. C. Douek, M. R. Betts, J. M. Brenchley et al., “A novel approach to the analysis of specificity, clonality, and frequency of HIV-specific T cell responses reveals a potential mechanism for control of viral escape,” Journal of Immunology, vol. 168, no. 6, pp. 3099–3104, 2002. View at Scopus
  88. L. Janbazian, D. A. Price, G. Canderan et al., “Clonotype and repertoire changes drive the functional improvement of HIV-specific CD8 T cell populations under conditions of limited antigenic stimulation,” Journal of Immunology, vol. 188, no. 3, pp. 1156–1167, 2012. View at Publisher · View at Google Scholar · View at Scopus
  89. K. P. J. M. van Gisbergen, P. L. Klarenbeek, N. A. M. Kragten et al., “The costimulatory molecule CD27 maintains clonally diverse CD8+ T cell responses of low antigen affinity to protect against viral variants,” Immunity, vol. 35, no. 1, pp. 97–108, 2011. View at Publisher · View at Google Scholar · View at Scopus
  90. S. Yang, J. W. Hodge, D. W. Grosenbach, and J. Schlom, “Vaccines with enhanced costimulation maintain high avidity memory CTL,” Journal of Immunology, vol. 175, no. 6, pp. 3715–3723, 2005. View at Scopus
  91. S. Oh, J. W. Hodge, J. D. Ahlers, D. S. Burke, J. Schlom, and J. A. Berzofsky, “Selective induction of high avidity CTL by altering the balance of signals from APC,” Journal of Immunology, vol. 170, no. 5, pp. 2523–2530, 2003. View at Scopus
  92. J. W. Hodge, M. Chakraborty, C. Kudo-Saito, C. T. Garnett, and J. Schlom, “Multiple costimulatory modalities enhance CTL avidity,” Journal of Immunology, vol. 174, no. 10, pp. 5994–6004, 2005. View at Scopus
  93. A. H. Sharpe, E. J. Wherry, R. Ahmed, and G. J. Freeman, “The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection,” Nature Immunology, vol. 8, no. 3, pp. 239–245, 2007. View at Publisher · View at Google Scholar · View at Scopus
  94. S. D. Blackburn, H. Shin, W. N. Haining et al., “Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection,” Nature Immunology, vol. 10, no. 1, pp. 29–37, 2009. View at Publisher · View at Google Scholar · View at Scopus
  95. W. Rees, J. Bender, T. K. Teague et al., “An inverse relationship between T cell receptor affinity and antigen dose during CD4+ T cell responses in vivo and in vitro,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 17, pp. 9781–9786, 1999. View at Publisher · View at Google Scholar · View at Scopus
  96. T. N. J. Bullock, D. W. Mullins, and V. H. Engelhard, “Antigen density presented by dendritic cells in vivo differentially affects the number and avidity of primary, memory, and recall CD8+ T cells,” Journal of Immunology, vol. 170, no. 4, pp. 1822–1829, 2003. View at Scopus
  97. M. A. Alexander-Miller, G. R. Leggatt, and J. A. Berzofsky, “Selective expansion of high- or low-avidity cytotoxic T lymphocytes and efficacy for adoptive immunotherapy,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 9, pp. 4102–4107, 1996. View at Publisher · View at Google Scholar · View at Scopus
  98. V. Levitsky, Q. J. Zhang, J. Levitskaya, and M. G. Masucci, “The life span of major histocompatibility complex-peptide complexes influences the efficiency of presentation and immunogenicity of two class I-restricted cytotoxic T lymphocyte epitopes in the Epstein-Barr virus nuclear antigen 4,” Journal of Experimental Medicine, vol. 183, no. 3, pp. 915–926, 1996. View at Scopus
  99. I. Galea, J. Stasakova, M. S. Dunscombe, C. H. Ottensmeier, T. Elliott, and S. M. Thirdborough, “CD8+ T-cell cross-competition is governed by peptide-MHC class I stability,” European Journal of Immunology, vol. 42, no. 1, pp. 256–263, 2012. View at Publisher · View at Google Scholar · View at Scopus
  100. D. Zehn, C. J. Cohen, Y. Reiter, and P. Walden, “Extended presentation of specific MHC-peptide complexes by mature dendritic cells compared to other types of antigen-presenting cells,” European Journal of Immunology, vol. 34, no. 6, pp. 1551–1560, 2004. View at Publisher · View at Google Scholar · View at Scopus
  101. T. Lövgren, P. Baumgaertner, S. Wieckowski et al., “Enhanced cytotoxicity and decreased CD8 dependence of human cancer-specific cytotoxic T lymphocytes after vaccination with low peptide dose,” Cancer Immunology, Immunotherapy, vol. 61, no. 6, pp. 817–826, 2012. View at Publisher · View at Google Scholar · View at Scopus
  102. M. R. Von Essen, M. Kongsbak, and C. Geisler, “Mechanisms behind functional avidity maturation in T cells,” Clinical and Developmental Immunology, vol. 2012, Article ID 163453, 8 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  103. P. A. Savage, J. J. Boniface, and M. M. Davis, “A kinetic basis for T cell receptor repertoire selection during an immune response,” Immunity, vol. 10, no. 4, pp. 485–492, 1999. View at Publisher · View at Google Scholar · View at Scopus
  104. D. Zehn, S. Y. Lee, and M. J. Bevan, “Complete but curtailed T-cell response to very low-affinity antigen,” Nature, vol. 458, no. 7235, pp. 211–214, 2009. View at Publisher · View at Google Scholar · View at Scopus
  105. M. F. Bachmann, D. E. Speiser, and P. S. Ohashi, “Functional maturation of an antiviral cytotoxic T-cell response,” Journal of Virology, vol. 71, no. 8, pp. 5764–5768, 1997. View at Scopus
  106. D. H. Busch and E. G. Pamer, “T cell affinity maturation by selective expansion during infection,” Journal of Experimental Medicine, vol. 189, no. 4, pp. 701–709, 1999. View at Publisher · View at Google Scholar · View at Scopus
  107. E. K. Day, A. J. Carmichael, I. J. M. Ten Berge, E. C. P. Waller, J. G. P. Sissons, and M. R. Wills, “Rapid CD8+ T cell repertoire focusing and selection of high-affinity clones into memory following primary infection with a persistent human virus: human cytomegalovirus,” Journal of Immunology, vol. 179, no. 5, pp. 3203–3213, 2007. View at Scopus
  108. G. Rechtsteiner, T. Warger, M. Hofmann, H. G. Rammensee, H. J. Schild, and M. P. Radsak, “Precursor frequency can compensate for lower TCR expression in T cell competition during priming in vivo,” European Journal of Immunology, vol. 36, no. 10, pp. 2613–2623, 2006. View at Publisher · View at Google Scholar · View at Scopus
  109. M. Pihlgren, P. M. Dubois, M. Tomkowiak, T. Sjögren, and J. Marvel, “Resting memory CD8+ T cells are hyperreactive to antigenic challenge in vitro,” Journal of Experimental Medicine, vol. 184, no. 6, pp. 2141–2151, 1996. View at Scopus
  110. J. M. Curtsinger, D. C. Lins, and M. F. Mescher, “CD8+ memory T cells (CD44high, Ly-6C+) are more sensitive than naive cells (CD44low, Ly-6C) to TCR/CD8 signaling in response to antigen,” Journal of Immunology, vol. 160, no. 7, pp. 3236–3243, 1998. View at Scopus
  111. B. Alarcón, D. Mestre, and N. Martínez-Martín, “The immunological synapse: a cause or consequence of T-cell receptor triggering?” Immunology, vol. 133, no. 4, pp. 420–425, 2011. View at Publisher · View at Google Scholar · View at Scopus
  112. T. Yokosuka and T. Saito, “Dynamic regulation of T-cell costimulation through TCR-CD28 microclusters,” Immunological Reviews, vol. 229, no. 1, pp. 27–40, 2009. View at Publisher · View at Google Scholar · View at Scopus
  113. T. M. Fahmy, J. G. Bieler, M. Edidin, and J. P. Schneck, “Increased TCR avidity after T cell activation: a mechanism for sensing low-density antigen,” Immunity, vol. 14, no. 2, pp. 135–143, 2001. View at Scopus
  114. A. T. Robinson, N. Miller, and D. R. Alexander, “CD3 antigen-mediated calcium signals and protein kinase C activation are higher in CD45RO+ than in CD45RA+ human T lymphocyte subsets,” European Journal of Immunology, vol. 23, no. 1, pp. 61–68, 1993. View at Publisher · View at Google Scholar · View at Scopus
  115. R. Schwinzer, R. Siefken, R. A. Franklin, J. Saloga, K. Wonigeit, and E. W. Gelfand, “Human CD45RA+ and CD45R0+ T cells exhibit similar CD3/T cell receptor-mediated transmembrane signaling capacities but differ in response to co-stimulatory signals,” European Journal of Immunology, vol. 24, no. 6, pp. 1391–1395, 1994. View at Publisher · View at Google Scholar · View at Scopus
  116. M. Croft, L. M. Bradley, and S. L. Swain, “Naive versus memory CD4 T cell response to antigen: memory cells are less dependent on accessory cell costimulation and can respond to many antigen- presenting cell types including resting B cells,” Journal of Immunology, vol. 152, no. 6, pp. 2675–2685, 1994. View at Scopus
  117. M. J. Turner, E. R. Jellison, E. G. Lingenheld, L. Puddington, and L. Lefrançois, “Avidity maturation of memory CD8 T cells is limited by self-antigen expression,” Journal of Experimental Medicine, vol. 205, no. 8, pp. 1859–1868, 2008. View at Publisher · View at Google Scholar · View at Scopus
  118. M. Lichterfeld, X. G. Yu, S. K. Mui et al., “Selective depletion of high-avidity human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T cells after early HIV-1 infection,” Journal of Virology, vol. 81, no. 8, pp. 4199–4214, 2007. View at Publisher · View at Google Scholar · View at Scopus
  119. V. Dutoit, V. Rubio-Godoy, P. Y. Dietrich et al., “Heterogeneous T-cell response to MAGE-A10254-262: high avidity-specific cytolytic T lymphocytes show superior antitumor activity,” Cancer Research, vol. 61, no. 15, pp. 5850–5856, 2001. View at Scopus
  120. J. T. Snyder, M. A. Alexander-Miller, J. A. Berzofskyl, and I. M. Belyakov, “Molecular mechanisms and biological significance of CTL avidity,” Current HIV Research, vol. 1, no. 3, pp. 287–294, 2003. View at Scopus
  121. C. T. Berger, N. Frahm, D. A. Price et al., “High-functional-avidity cytotoxic T lymphocyte responses to HLA-B-restricted gag-derived epitopes associated with relative HIV control,” Journal of Virology, vol. 85, no. 18, pp. 9334–9345, 2011. View at Publisher · View at Google Scholar · View at Scopus
  122. T. Kitazono, T. Okazaki, N. Araya et al., “Advantage of higher-avidity CTL specific for Tax against human T-lymphotropic virus-1 infected cells and tumors,” Cellular Immunology, vol. 272, no. 1, pp. 11–17, 2011. View at Publisher · View at Google Scholar · View at Scopus
  123. R. H. McMahan and J. E. Slansky, “Mobilizing the low-avidity T cell repertoire to kill tumors,” Seminars in Cancer Biology, vol. 17, no. 4, pp. 317–329, 2007. View at Publisher · View at Google Scholar · View at Scopus
  124. D. Zehn and M. J. Bevan, “T cells with low avidity for a tissue-restricted antigen routinely evade central and peripheral tolerance and cause autoimmunity,” Immunity, vol. 25, no. 2, pp. 261–270, 2006. View at Publisher · View at Google Scholar · View at Scopus
  125. J. M. Kirkwood, L. H. Butterfield, A. A. Tarhini, H. Zarour, P. Kalinski, and S. Ferrone, “Immunotherapy of cancer in 2012,” CA Cancer Journal for Clinicians, vol. 62, no. 5, pp. 309–335, 2012. View at Publisher · View at Google Scholar · View at Scopus
  126. C. H. June, “Adoptive T cell therapy for cancer in the clinic,” Journal of Clinical Investigation, vol. 117, no. 6, pp. 1466–1476, 2007. View at Publisher · View at Google Scholar · View at Scopus
  127. M. S. Bennett, H. L. Ng, M. Dagarag, A. Ali, and O. O. Yang, “Epitope-dependent avidity thresholds for cytotoxic T-lymphocyte clearance of virus-infected cells,” Journal of Virology, vol. 81, no. 10, pp. 4973–4980, 2007. View at Publisher · View at Google Scholar · View at Scopus
  128. I. M. Belyakov, V. A. Kuznetsov, B. Kelsall et al., “Impact of vaccine-induced mucosal high-avidity CD8+CTLs in delay of AIDS viral dissemination from mucosa,” Blood, vol. 107, no. 8, pp. 3258–3264, 2006. View at Publisher · View at Google Scholar · View at Scopus
  129. H. J. Zeh Jr., D. Perry-Lalley, M. E. Dudley, S. A. Rosenberg, and J. C. Yang, “High avidity CTLs for two self-antigens demonstrate superior in vitro and in vivo antitumor efficacy,” Journal of Immunology, vol. 162, no. 2, pp. 989–994, 1999. View at Scopus
  130. F. Aranda, D. Llopiz, N. Díaz-Valdés et al., “Adjuvant combination and antigen targeting as a strategy to induce polyfunctional and high-avidity T-cell responses against poorly immunogenic tumors,” Cancer Research, vol. 71, no. 9, pp. 3214–3224, 2011. View at Publisher · View at Google Scholar · View at Scopus
  131. M. A. Derby, M. A. Alexander-Miller, R. Tse, and J. A. Berzofsky, “High-avidity CTL exploit two complementary mechanisms to provide better protection against viral infection than low-avidity CTL,” Journal of Immunology, vol. 166, no. 3, pp. 1690–1697, 2001. View at Scopus
  132. B. Jessen, S. Faller, C. D. Krempl, and S. Ehl, “Major histocompatibility complex-dependent cytotoxic T lymphocyte repertoire and functional avidity contribute to strain-specific disease susceptibility after murine respiratory syncytial virus infection,” Journal of Virology, vol. 85, no. 19, pp. 10135–10143, 2011. View at Publisher · View at Google Scholar · View at Scopus
  133. A. Košmrlj, E. L. Read, Y. Qi et al., “Effects of thymic selection of the T-cell repertoire on HLA class I-associated control of HIV infection,” Nature, vol. 465, no. 7296, pp. 350–354, 2010. View at Publisher · View at Google Scholar · View at Scopus
  134. A. Leslie, D. A. Price, P. Mkhize et al., “Differential selection pressure exerted on HIV by CTL targeting identical epitopes but restricted by distinct HLA alleles from the same HLA supertype,” Journal of Immunology, vol. 177, no. 7, pp. 4699–4708, 2006. View at Scopus
  135. J. R. Almeida, D. Sauce, D. A. Price et al., “Antigen sensitivity is a major determinant of CD8+ T-cell polyfunctionality and HIV-suppressive activity,” Blood, vol. 113, no. 25, pp. 6351–6360, 2009. View at Publisher · View at Google Scholar · View at Scopus
  136. D. J. Morgan, H. T. C. Kreuwel, S. Fleck, H. I. Levitsky, D. M. Pardoll, and L. A. Sherman, “Activation of low avidity CTL specific for a self epitope results in tumor rejection but not autoimmunity,” Journal of Immunology, vol. 160, no. 2, pp. 643–651, 1998. View at Scopus
  137. A. Wankowicz-Kalinska, R. B. Mailliard, K. Olson et al., “Accumulation of low-avidity anti-melanocortin receptor 1 (anti-MC1R) CD8+ T cells in the lesional skin of a patient with melanoma-related depigmentation,” Melanoma Research, vol. 16, no. 2, pp. 165–174, 2006. View at Publisher · View at Google Scholar · View at Scopus
  138. S. M. Anderton, C. G. Radu, P. A. Lowrey, E. S. Ward, and D. C. Wraith, “Negative selection during the peripheral immune response to antigen,” Journal of Experimental Medicine, vol. 193, no. 1, pp. 1–11, 2001. View at Publisher · View at Google Scholar · View at Scopus
  139. M. C. Iglesias, J. R. Almeida, S. Fastenackels et al., “Escape from highly effective public CD8+ T-cell clonotypes by HIV,” Blood, vol. 118, no. 8, pp. 2138–2149, 2011. View at Publisher · View at Google Scholar · View at Scopus
  140. D. A. Price, J. M. Brenchley, L. E. Ruff et al., “Avidity for antigen shapes clonal dominance in CD8+ T cell populations specific for persistent DNA viruses,” Journal of Experimental Medicine, vol. 202, no. 10, pp. 1349–1361, 2005. View at Publisher · View at Google Scholar · View at Scopus
  141. J. A. Conrad, R. K. Ramalingam, R. M. Smith et al., “Dominant clonotypes within HIV-specific T cell responses are programmed death-1highand CD127lowand display reduced variant cross-reactivity,” Journal of Immunology, vol. 186, no. 12, pp. 6871–6885, 2011. View at Publisher · View at Google Scholar · View at Scopus
  142. T. Miura, C. J. Brumme, M. A. Brockman et al., “HLA-associated viral mutations are common in human immunodeficiency virus type 1 elite controllers,” Journal of Virology, vol. 83, no. 7, pp. 3407–3412, 2009. View at Publisher · View at Google Scholar · View at Scopus
  143. S. A. Migueles, A. C. Laborico, H. Imamichi et al., “The differential ability of HLA B*5701+ long-term nonprogressors and progressors to restrict human immunodeficiency virus replication is not caused by loss of recognition of autologous viral gag sequences,” Journal of Virology, vol. 77, no. 12, pp. 6889–6898, 2003. View at Publisher · View at Google Scholar · View at Scopus
  144. S. A. Migueles, A. C. Laborico, W. L. Shupert et al., “HIV-specific CD8+ T cell proliferation is coupled to perforin expression and is maintained in nonprogressors,” Nature Immunology, vol. 3, no. 11, pp. 1061–1068, 2002. View at Publisher · View at Google Scholar · View at Scopus
  145. R. Draenert, C. L. Verrill, Y. Tang et al., “Persistent recognition of autologous virus by high-avidity CD8 T cells in chronic, progressive human immunodeficiency virus type 1 infection,” Journal of Virology, vol. 78, no. 2, pp. 630–641, 2004. View at Publisher · View at Google Scholar · View at Scopus
  146. J. R. Bailey, T. M. Williams, R. F. Siliciano, and J. N. Blankson, “Maintenance of viral suppression in HIV-1-infected HLA-B*57+ elite suppressors despite CTL escape mutations,” Journal of Experimental Medicine, vol. 203, no. 5, pp. 1357–1369, 2006. View at Publisher · View at Google Scholar · View at Scopus
  147. C. T. Berger, N. Frahm, D. A. Price et al., “High-functional-avidity cytotoxic T lymphocyte responses to HLA-B-restricted gag-derived epitopes associated with relative HIV control,” Journal of Virology, vol. 85, no. 18, pp. 9334–9345, 2011. View at Publisher · View at Google Scholar · View at Scopus
  148. B. Mothe, A. Llano, J. Ibarrondo et al., “Ctl responses of high functional avidity and broad variant cross-reactivity are associated with hiv control,” PLoS One, vol. 7, no. 1, Article ID e29717, 2012. View at Publisher · View at Google Scholar · View at Scopus
  149. P. Kiepiela, K. Ngumbela, C. Thobakgale et al., “CD8+ T-cell responses to different HIV proteins have discordant associations with viral load,” Nature Medicine, vol. 13, no. 1, pp. 46–53, 2007. View at Publisher · View at Google Scholar · View at Scopus
  150. D. Y. Chen, A. Balamurugan, H. L. Ng, W. G. Cumberland, and O. O. Yang, “Epitope targeting and viral inoculum are determinants of Nef-mediated immune evasion of HIV-1 from cytotoxic T lymphocytes,” Blood, vol. 120, no. 1, pp. 100–111, 2012. View at Publisher · View at Google Scholar · View at Scopus
  151. N. M. Keane, S. G. Roberts, C.-A. M. Almeida et al., “High-avidity, high-IFNγ-producing CD8 T-cell responses following immune selection during HIV-1 infection,” Immunology and Cell Biology, vol. 90, no. 2, pp. 224–234, 2012. View at Publisher · View at Google Scholar · View at Scopus
  152. H. Chen, Z. M. Ndhlovu, D. Liu et al., “TCR clonotypes modulate the protective effect of HLA class I molecules in HIV-1 infection,” Nature Immunology, vol. 13, no. 7, pp. 691–700, 2012. View at Publisher · View at Google Scholar · View at Scopus
  153. T. Ueno, H. Tomiyama, M. Fujiwara, S. Oka, and M. Takiguchi, “Functionally impaired HIV-specific CD8 T cells show high affinity TCR-ligand interactions,” Journal of Immunology, vol. 173, no. 9, pp. 5451–5457, 2004. View at Scopus
  154. Y. Kamari, R. Werman-Venkert, A. Shaish et al., “Differential role and tissue specificity of interleukin-1α gene expression in atherogenesis and lipid metabolism,” Atherosclerosis, vol. 195, no. 1, pp. 31–38, 2007. View at Publisher · View at Google Scholar · View at Scopus
  155. N. Chomont, M. El-Far, P. Ancuta et al., “HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation,” Nature Medicine, vol. 15, no. 8, pp. 893–900, 2009. View at Publisher · View at Google Scholar · View at Scopus
  156. E. J. Wherry, S. J. Ha, S. M. Kaech et al., “Molecular signature of CD8+ T cell exhaustion during chronic viral infection,” Immunity, vol. 27, no. 4, pp. 670–684, 2007. View at Publisher · View at Google Scholar · View at Scopus
  157. G. P. Rizzardi, A. Harari, B. Capiluppi et al., “Treatment of primary HIV-1 infection with cyclosporin A coupled with highly active antiretroviral therapy,” Journal of Clinical Investigation, vol. 109, no. 5, pp. 681–688, 2002. View at Publisher · View at Google Scholar · View at Scopus