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Predicting Cross-Reactivity and Antigen Specificity of T Cell Receptors

Chloe H Lee1,2, Mariolina Salio1, Giorgio Napolitani1

  • 1MRC Human Immunology Unit, Medical Research Council (MRC) Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.

Frontiers in Immunology
|November 16, 2020
PubMed

Adaptive immune recognition is mediated by specific interactions between heterodimeric T cell receptors (TCRs) and their cognate peptide-MHC (pMHC) ligands, and the methods to accurately predict TCR:pMHC interaction would have profound clinical, therapeutic and pharmaceutical applications. Herein, we review recent developments in predicting cross-reactivity and antigen specificity of TCR recognition. We discuss current experimental and computational approaches to investigate cross-reactivity and antigen-specificity of TCRs and highlight how integrating kinetic, biophysical and structural features may offer valuable insights in modeling immunogenicity. We further underscore the close inter-relationship of these two interconnected notions and the need to investigate each in the light of the other for a better understanding of T cell responsiveness for the effective clinical applications.

Keywords:
T cell cross reactivityT cell specificityadaptive immune systemantigen presentationantigen specificityepitope

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