Learning predictive signatures of HLA type from T-cell repertoires.

T cells recognize a wide range of pathogens using surface receptors that interact directly with peptides presented on major histocompatibility complexes (MHC) encoded by the HLA loci in humans. Understanding the association between T cell receptors (TCR) and HLA alleles is an important step towards predicting TCR-antigen specificity from sequences. Here we analyze the TCR alpha and beta repertoires of large cohorts of HLA-typed donors to systematically infer such associations, by looking for overrepresentation of TCRs in individuals with a common allele.

DNAJB1-PRKACA fusion neoantigens elicit rare endogenous T cell responses that potentiate cell therapy for fibrolamellar carcinoma.

Fibrolamellar carcinoma (FLC) is a liver tumor with a high mortality burden and few treatment options. A promising therapeutic vulnerability in FLC is its driver mutation, a conserved DNAJB1-PRKACA gene fusion that could be an ideal target neoantigen for immunotherapy. In this study, we aim to define endogenous CD8 T cell responses to this fusion in FLC patients and evaluate fusion-specific T cell receptors (TCRs) for use in cellular immunotherapies.

Learning predictive signatures of HLA type from T-cell repertoires.

T cells recognize a wide range of pathogens using surface receptors that interact directly with pep-tides presented on major histocompatibility complexes (MHC) encoded by the HLA loci in humans. Understanding the association between T cell receptors (TCR) and HLA alleles is an important step towards predicting TCR-antigen specificity from sequences. Here we analyze the TCR alpha and beta repertoires of large cohorts of HLA-typed donors to systematically infer such associations, by looking for overrepresentation of TCRs in individuals with a common allele.

copepodTCR: Identification of Antigen-Specific T Cell Receptors with combinatorial peptide pooling.

T cell receptor (TCR) repertoire diversity enables the orchestration of antigen-specific immune responses against the vast space of possible pathogens. Identifying TCR/antigen binding pairs from the large TCR repertoire and antigen space is crucial for biomedical research. Here, we introduce , an open-access tool for the design and interpretation of high-throughput experimental assays to determine TCR specificity.