Emerging Concepts in TCR Specificity: Rationalizing and (Maybe) Predicting Outcomes
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 PharmacologyProgram in Bioinformatics and Integrative Biology
Document Type
Journal ArticlePublication Date
2017-10-01Keywords
Biochemistry, Biophysics, and Structural BiologyBioinformatics
Computational Biology
Immunology and Infectious Disease
Integrative Biology
Systems Biology
Metadata
Show full item recordAbstract
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 siteDOI
10.4049/jimmunol.1700744Permanent Link to this Item
http://hdl.handle.net/20.500.14038/25831PubMed ID
28923982Related Resources
ae974a485f413a2113503eed53cd6c53
10.4049/jimmunol.1700744