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Critical Reviews™ in Immunology
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ISSN Print: 1040-8401
ISSN Online: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.2020034838
Forthcoming Article

Aleatory epitope recognition prevails in human T cell responses?

Paul Lehmann
Cellular Technology Ltd.
Alexander Lehmann
Cellular Technology Ltd.


Eli Sercarz pioneered epitope recognition by T cells. Studying mice, he made the seminal observation decades ago that epitope dominance is so unpredictable with mixed MHC haplotypes that he coined it aleatory, for dice-like. Accordingly, for every individual there is a potential epitope space that is defined by the polymorphic and polygenic MHC molecules (restriction elements) they express. Of this potential epitope space, some peptides will elicit stronger T cell responses than others, bringing about the actually realized epitope space. The selection of the actually recognized peptides from the potential epitope space is random, however, resulting in unique epitope dominance and hierarchy patterns in individuals. Engaging in brute force epitope scans, permits the assessment of the entire potential epitope space at the highest possible resolution, we observe aleatory epitope recognition in human CD8 cell responses to viruses. Because this notion has fundamental implications for T cell immune monitoring, we dedicate this article to Eli Sercarz in a special issue of Critical Reviews in Immunology in his honor. Every scientist stands on the shoulders of the giants who taught him/her. For me (PVL), Eli Sercarz was one of these giants, (Zoltan A. Nagy being the other), to whom I owe major credit. I am one of those blessed immunologists whose child has not been repelled by experiencing the craze of two scientist parents’ daily life (or perhaps the lack of a life beyond science) and who also chose to follow the same path. By standing on my shoulders, my son, Alex (AL), therefore also stands on Eli’s. Alex’s PhD thesis is in a field that Eli pioneered, immune monitoring