In the process of VDJ recombination, a huge diversity of TCR sequences are generated, arming T cells with the ability to recognize a multitude of targets. The recognition process takes place when the TCR engages its cognate epitopes, short peptides presented on HLA molecules. The specificity of this interaction makes TCRs an attractive platform for developing targeted therapeutics or diagnostics. However, a bottleneck to such applications lies in the enormous diversity of TCRs and potential peptide-HLA pairs, which hinders efforts at determining specificity and potential cross-reactivity. In this research topic, we aim to dive deeply into the space between TCR and its cognate epitope: We invite submissions exploring the link of a specific TCR sequence to a cognate antigen or how that link could be harnessed to develop therapeutics/diagnostics in human disease. Recent advances in this domain including cryo-EM structures of the TCR-pMHC complex, single-cell TCR sequencing, and multiplexed methods for determining specific TCRs, allow us to start delineating the rules of epitope recognition. Here, we aim to assemble primary research articles and reviews highlighting some of the most exciting developments in this area. However, Original Research, Systematic Review, Review, Mini Review, Methods, Hypothesis and Theory, Perspective, Clinical Trials, Case reports, Conceptual Analysis, Data reports, Technology, and Code articles will be accepted in this research topic.Specific examples of areas of research that would be highly suitable for the research topic include (but are not limited to):• Methods to link TCRs with their cognate antigens (throughput, validation, etc)• Molecular and/or structural insight into TCR-pMHC interactions• Computational methods for learning the sequence determinants of TCR specificity• Engineered cellular therapies based on TCR specificity - neoantigen directed T cell therapies in cancer (personalized or not) / Treg cell therapies in autoimmunity• T-cell directed vaccination strategies, e.g. for cancer immunotherapy• Soluble TCR approaches based on TCRs-pMHC data• TCR repertoires as high-dimensional immunodiagnostics• TCR specificity discovery as a way to identify 'holes' in pathogen immune evasion
In the process of VDJ recombination, a huge diversity of TCR sequences are generated, arming T cells with the ability to recognize a multitude of targets. The recognition process takes place when the TCR engages its cognate epitopes, short peptides presented on HLA molecules. The specificity of this interaction makes TCRs an attractive platform for developing targeted therapeutics or diagnostics. However, a bottleneck to such applications lies in the enormous diversity of TCRs and potential peptide-HLA pairs, which hinders efforts at determining specificity and potential cross-reactivity. In this research topic, we aim to dive deeply into the space between TCR and its cognate epitope: We invite submissions exploring the link of a specific TCR sequence to a cognate antigen or how that link could be harnessed to develop therapeutics/diagnostics in human disease. Recent advances in this domain including cryo-EM structures of the TCR-pMHC complex, single-cell TCR sequencing, and multiplexed methods for determining specific TCRs, allow us to start delineating the rules of epitope recognition. Here, we aim to assemble primary research articles and reviews highlighting some of the most exciting developments in this area. However, Original Research, Systematic Review, Review, Mini Review, Methods, Hypothesis and Theory, Perspective, Clinical Trials, Case reports, Conceptual Analysis, Data reports, Technology, and Code articles will be accepted in this research topic.Specific examples of areas of research that would be highly suitable for the research topic include (but are not limited to):• Methods to link TCRs with their cognate antigens (throughput, validation, etc)• Molecular and/or structural insight into TCR-pMHC interactions• Computational methods for learning the sequence determinants of TCR specificity• Engineered cellular therapies based on TCR specificity - neoantigen directed T cell therapies in cancer (personalized or not) / Treg cell therapies in autoimmunity• T-cell directed vaccination strategies, e.g. for cancer immunotherapy• Soluble TCR approaches based on TCRs-pMHC data• TCR repertoires as high-dimensional immunodiagnostics• TCR specificity discovery as a way to identify 'holes' in pathogen immune evasion