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Journal of Immunology Research
Volume 2017 (2017), Article ID 2748614, 12 pages
https://doi.org/10.1155/2017/2748614
Research Article

The Immunogenicity of HLA Class II Mismatches: The Predicted Presentation of Nonself Allo-HLA-Derived Peptide by the HLA-DR Phenotype of the Recipient Is Associated with the Formation of DSA

Terasaki Foundation Laboratory, 11570 W Olympic Blvd., Los Angeles, CA 90064, USA

Correspondence should be addressed to Vadim Jucaud; gro.balikasaret@duacujv

Received 29 October 2016; Revised 17 January 2017; Accepted 2 February 2017; Published 26 February 2017

Academic Editor: Frans H. J. Claas

Copyright © 2017 Vadim Jucaud. 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.

Abstract

The identification of permissible HLA class II mismatches can prevent DSA in mismatched transplantation. The HLA-DR phenotype of recipients contributes to DSA formation by presenting allo-HLA-derived peptides to T-helper cells, which induces the differentiation of B cells into plasma cells. Comparing the binding affinity of self and nonself allo-HLA-derived peptides for recipients’ HLA class II antigens may distinguish immunogenic HLA mismatches from nonimmunogenic ones. The binding affinities of allo-HLA-derived peptides to recipients’ HLA-DR and HLA-DQ antigens were predicted using the NetMHCIIpan 3.1 server. HLA class II mismatches were classified based on whether they induced DSA and whether self or nonself peptide was predicted to bind with highest affinity to recipients’ HLA-DR and HLA-DQ. Other mismatch characteristics (eplet, hydrophobic, electrostatic, and amino acid mismatch scores and PIRCHE-II) were evaluated. A significant association occurred between DSA formation and the predicted HLA-DR presentation of nonself peptides (; accuracy = 80%; sensitivity = 88%; specificity = 63%). In contrast, mismatch characteristics did not differ significantly between mismatches that induced DSA and the ones that did not, except for PIRCHE-II (). This methodology predicts DSA formation based on HLA mismatches and recipients’ HLA-DR phenotype and may identify permissible HLA mismatches to help optimize HLA matching and guide donor selection.