AUTHOR=Ghoreyshi Zahra S. , George Jason T. TITLE=Quantitative approaches for decoding the specificity of the human T cell repertoire JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1228873 DOI=10.3389/fimmu.2023.1228873 ISSN=1664-3224 ABSTRACT=

T cell receptor (TCR)-peptide-major histocompatibility complex (pMHC) interactions play a vital role in initiating immune responses against pathogens, and the specificity of TCRpMHC interactions is crucial for developing optimized therapeutic strategies. The advent of high-throughput immunological and structural evaluation of TCR and pMHC has provided an abundance of data for computational approaches that aim to predict favorable TCR-pMHC interactions. Current models are constructed using information on protein sequence, structures, or a combination of both, and utilize a variety of statistical learning-based approaches for identifying the rules governing specificity. This review examines the current theoretical, computational, and deep learning approaches for identifying TCR-pMHC recognition pairs, placing emphasis on each method’s mathematical approach, predictive performance, and limitations.