TCR2HLA: Calibrated inference of HLA genotypes from TCR repertoires enables identification of immunologically relevant metaclonotypes.

ABSTRACT: T cell receptors (TCRs) recognize peptides presented by polymorphic human leukocyte antigen (HLA) molecules, but HLA genotype data are often missing from TCR repertoire sequencing studies. To address this, we developed TCR2HLA, an open-source tool that infers HLA genotypes from TCRβ repertoires. Expanding on work linking public TRBV-CDR3 sequences to HLA genotypes, we incorporated "quasi-public" metaclonotypes - composed of rarer TCRβ sequences with shared amino acid features - enriched by HLA genotypes. Using four TCRβseq datasets from 3,150 individuals, we applied TRBV gene partitioning and locality-sensitive hashing to identify ~96,000 TCRβ features strongly associated with specific HLA alleles from 71M input TCRs. Binary HLA classifiers built with these features achieved high balanced

SUBMITTER: Mayer-Blackwell K 

PROVIDER: S-EPMC12810895 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature