Large-scale statistical mapping of T-cell receptor β sequences to Human Leukocyte Antigens
Zahid, H. J.; Taniguchi, R.; Ebert, P.; Chow, I.-T.; Gooley, C.; Lv, J.; Pisani, L.; Rusnak, M.; Elyanow, R.; Takamatsu, H.; Zhou, W.; Greissl, J.; Robins, H.; Carlson, J. M.
Show abstract
T-cell receptors (TCRs) interacting with peptides presented by human leukocyte antigens (HLAs) are the foundation of the adaptive immune system but population-level analysis of TCR-HLA interactions is lacking. Here we statistically associate[~] 106 public TCRs to specific HLAs using the TCR{beta} repertoires sampled from 4,144 HLA-genotyped subjects. The TCRs we associate are specific to unique HLA allotypes, not allelic groups, and to the paired -{beta} heterodimer of class II HLAs though exceptions are observed. This specificity permits highly accurate imputation of 248 class I and II HLAs from the TCR{beta} repertoire. Notably, 45 HLA-DP and -DQ heterodimers lack associated TCRs because they likely arise from non-functional trans-complementation. The public class I and II HLA-associated TCRs we identify are primarily expressed on CD8+ and CD4+ memory T cells, respectively, which are responding to various common antigens. Our results recapitulate fundamental biology, provide insights into the functionality of HLAs and demonstrate the power and potential of population-level TCR repertoire sequencing.
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