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Journal of Biomedicine and Biotechnology
Volume 2010, Article ID 907092, 8 pages
Review Article

The Emerging Role of HLA-E-Restricted CD8+ T Lymphocytes in the Adaptive Immune Response to Pathogens and Tumors

1Dipartimento di Medicina Sperimentale and Centro di Eccellenza per le Ricerche Biomediche, Università degli Studi di Genova, 16132 Genova, Italy
2Clinical Immunology Group, German Rheumatism Research Centre, 10117 Berlin, Germany
3Istituto Giannina Gaslini, 16147 Genova, Italy
4Istituto Nazionale per la Ricerca sul Cancro, 16132 Genova, Italy

Received 14 January 2010; Accepted 4 May 2010

Academic Editor: Zhengguo Xiao

Copyright © 2010 Gabriella Pietra 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.


Human leukocyte antigen (HLA)-E is a nonclassical major histocompatibility complex (MHC) class I molecule of limited sequence variability that is expressed by most tissues albeit at low levels. HLA-E has been first described as the ligand of CD94/NKG2 receptors expressed mainly by natural killer (NK) cells, thus confining its role to the regulation of NK-cell function. However, recent evidences obtained by our and other groups indicate that HLA-E complexed with peptides can interact with T-cell receptor (TCR) expressed on CD8+ T cells. Although, HLA-E displays a selective preference for nonameric peptides, derived from the leader sequence of various HLA class I alleles, several reports indicate that it can present also “noncanonical” peptides derived from both stress-related and pathogen-associated proteins. Because HLA-E displays binding specificity for innate CD94/NKG2 receptors, as well as all the features of an antigen-presenting molecule, its role in both natural and acquired immune responses has recently been re-evaluated.