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Commun Biol . T cell receptor clonotypes predict human leukocyte antigen allele carriage and antigen exposure history

tetano

Editor, Senior Moderator
Commun Biol


. 2026 Jan 13;9(1):50.
doi: 10.1038/s42003-025-09140-2. T cell receptor clonotypes predict human leukocyte antigen allele carriage and antigen exposure history

Hesham ElAbd[SUP] #[/SUP][SUP] 1 2 [/SUP], Aya K H Mahdy[SUP] #[/SUP][SUP] 1 [/SUP], Eike Matthias Wacker[SUP] 1 [/SUP], Maria Gretsova[SUP] 1 [/SUP], David Ellinghaus[SUP] 1 [/SUP], Astrid Dempfile[SUP] 3 [/SUP], Andre Franke[SUP] 4 [/SUP]



Affiliations
Abstract

Conventional T cells recognize peptides presented by the human leukocyte antigen (HLA) proteins through their T cell receptors (TCRs). Given that thousands of HLA proteins have been discovered, each presenting thousands of different peptides, decoding the cognate HLA protein of a TCR experimentally is a challenging task. To address this problem, we combined statistical learning methods with a unique dataset of paired T cell repertoires and HLA allotypes for 6,794 individuals. This enabled us to discover 34,206 T cell receptor alpha (TRA) and 891,564 beta (TRB) clonotypes that were associated with 175 unique HLA alleles. The identified clonotypes target prevalent infections, e.g. influenza, cytomegalovirus and Epstein-Barr virus. Utilizing these clonotypes, we develop statistical models that impute the carriership of common HLA alleles from the TRA- or the TRB- repertoire. In conclusion, the identified allele-associated clonotypes encode the HLA fingerprints and the antigenic exposure history of individuals and populations.


 
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