Combining genotypes and T cell receptor distributions to infer genetic loci determining V(D)J recombination probabilities.

ABSTRACT: Every T cell receptor (TCR) repertoire is shaped by a complex probabilistic tangle of genetically determined biases and immune exposures. T cells combine a random V(D)J recombination process with a selection process to generate highly diverse and functional TCRs. The extent to which an individual's genetic background is associated with their resulting TCR repertoire diversity has yet to be fully explored. Using a previously published repertoire sequencing dataset paired with high-resolution genome-wide genotyping from a large human cohort, we infer specific genetic loci associated with V(D)J recombination probabilities using genome-wide association inference. We show that V(D)J gene usage profiles are associated with variation in the TCRB locus and, specifically for the functional T

SUBMITTER: Russell ML 

PROVIDER: S-EPMC8940181 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature