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    Emerging Concepts in TCR Specificity: Rationalizing and (Maybe) Predicting Outcomes

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    Authors
    Singh, Nishant K.
    Riley, Timothy P.
    Baker, Sarah Catherine B.
    Borrman, Tyler M.
    Weng, Zhiping
    Baker, Brian M.
    UMass Chan Affiliations
    Department of Biochemistry and Molecular Pharmacology
    Program in Bioinformatics and Integrative Biology
    Document Type
    Journal Article
    Publication Date
    2017-10-01
    Keywords
    Biochemistry, Biophysics, and Structural Biology
    Bioinformatics
    Computational Biology
    Immunology and Infectious Disease
    Integrative Biology
    Systems Biology
    
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    Link to Full Text
    https://doi.org/10.4049/jimmunol.1700744
    Abstract
    T cell specificity emerges from a myriad of processes, ranging from the biological pathways that control T cell signaling to the structural and physical mechanisms that influence how TCRs bind peptides and MHC proteins. Of these processes, the binding specificity of the TCR is a key component. However, TCR specificity is enigmatic: TCRs are at once specific but also cross-reactive. Although long appreciated, this duality continues to puzzle immunologists and has implications for the development of TCR-based therapeutics. In this review, we discuss TCR specificity, emphasizing results that have emerged from structural and physical studies of TCR binding. We show how the TCR specificity/cross-reactivity duality can be rationalized from structural and biophysical principles. There is excellent agreement between predictions from these principles and classic predictions about the scope of TCR cross-reactivity. We demonstrate how these same principles can also explain amino acid preferences in immunogenic epitopes and highlight opportunities for structural considerations in predictive immunology.
    Source
    J Immunol. 2017 Oct 1;199(7):2203-2213. doi: 10.4049/jimmunol.1700744. Link to article on publisher's site
    DOI
    10.4049/jimmunol.1700744
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/25831
    PubMed ID
    28923982
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    Link to Article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.4049/jimmunol.1700744
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