Emerging Concepts in TCR Specificity: Rationalizing and (Maybe) Predicting Outcomes
AuthorsSingh, Nishant K.
Riley, Timothy P.
Baker, Sarah Catherine B.
Borrman, Tyler M.
Baker, Brian M.
UMass Chan AffiliationsDepartment of Biochemistry and Molecular Pharmacology
Program in Bioinformatics and Integrative Biology
Document TypeJournal Article
KeywordsBiochemistry, Biophysics, and Structural Biology
Immunology and Infectious Disease
MetadataShow full item record
AbstractT 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.
SourceJ Immunol. 2017 Oct 1;199(7):2203-2213. doi: 10.4049/jimmunol.1700744. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/25831