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Allo‐ HLA Cross‐Reactivities of Cytomegalovirus‐, Influenza‐, and Varicella Zoster Virus–Specific Memory T Cells Are Shared by Different Healthy Individuals
Author(s) -
Heuvel H.,
Heutinck K. M.,
MeerPrins E. M. W.,
Yong S. L.,
Miert P. P. M. C.,
Anholts J. D. H.,
Frankevan Dijk M. E. I.,
Zhang X. Q.,
Roelen D. L.,
Berge R. J. M.,
Claas F. H. J.
Publication year - 2017
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.14279
Subject(s) - immunology , human leukocyte antigen , cytotoxic t cell , virology , cd8 , cross reactivity , virus , transplantation , biology , medicine , antigen , in vitro , genetics , surgery , cross reactions
Virus‐specific T cells can recognize allogeneic HLA (allo‐ HLA ) through TCR cross‐reactivity. The allospecificity often differs by individual ( private cross‐reactivity) but also can be shared by multiple individuals ( public cross‐reactivity); however, only a few examples of the latter have been described. Because these could facilitate alloreactivity prediction in transplantation, we aimed to identify novel public cross‐reactivities of human virus‐specific CD 8 + T cells directed against allo‐ HLA by assessing their reactivity in mixed‐lymphocyte reactions. Further characterization was done by studying TCR usage with primer‐based DNA sequencing, cytokine production with ELISA s, and cytotoxicity with 51 chromium‐release assays. We identified three novel public allo‐ HLA cross‐reactivities of human virus‐specific CD 8 + T cells. CMV B35/ IPS CD 8 + T cells cross‐reacted with HLA ‐B51 and/or HLA ‐B58/B57 (23% of tetramer‐positive individuals), FLU A2/ GIL (influenza IMP [58‐66] HLA ‐A*02:01/ GILGFVFTL ) CD 8 + T cells with HLA ‐B38 (90% of tetramer‐positive individuals), and VZV A2/ ALW (varicella zoster virus IE 62[593‐601] HLA ‐A*02:01/ ALWALPHAA ) CD 8 + T cells with HLA ‐B55 (two unrelated individuals). Cross‐reactivity was tested against different cell types including endothelial and epithelial cells. All cross‐reactive T cells expressed a memory phenotype, emphasizing the importance for transplantation. We conclude that public allo‐ HLA cross‐reactivity of virus‐specific memory T cells is not uncommon and may create novel opportunities for alloreactivity prediction and risk estimation in transplantation.