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Human TCR-binding affinity is governed by MHC class restriction

Cole, David ORCID: https://orcid.org/0000-0003-0028-9396, Pumphrey, Nicholas J., Boulter, Jonathan M., Sami, Malkit, Bell, John I., Gostick, Emma, Price, David ORCID: https://orcid.org/0000-0001-9416-2737, Gao, George F., Sewell, Andrew K. ORCID: https://orcid.org/0000-0003-3194-3135 and Jakobsen, Bent K. 2007. Human TCR-binding affinity is governed by MHC class restriction. The Journal of Immunology 178 (9) , pp. 5727-5734. 10.4049/​jimmunol.178.9.5727

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Abstract

T cell recognition is initiated by the binding of TCRs to peptide-MHCs (pMHCs), the interaction being characterized by weak affinity and fast kinetics. Previously, only 16 natural TCR/pMHC interactions have been measured by surface plasmon resonance (SPR). Of these, 5 are murine class I, 5 are murine class II, and 6 are human class I-restricted responses. Therefore, a significant gap exists in our understanding of human TCR/pMHC binding due to the limited SPR data currently available for human class I responses and the absence of SPR data for human class II-restricted responses. We have produced a panel of soluble TCR molecules originating from human T cells that respond to naturally occurring disease epitopes and their cognate pMHCs. In this study, we compare the binding affinity and kinetics of eight class-I-specific TCRs (TCR-Is) to pMHC-I with six class-II-specific TCRs (TCR-IIs) to pMHC-II using SPR. Overall, there is a substantial difference in the TCR-binding equilibrium constants for pMHC-I and pMHC-II, which arises from significantly faster on-rates for TCRs binding to pMHC-I. In contrast, the off-rates for all human TCR/pMHC interactions fall within a narrow window regardless of class restriction, thereby providing experimental support for the notion that binding half-life is the principal kinetic feature controlling T cell activation.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Publisher: American Association of Immunologists
ISSN: 0022-1767
Last Modified: 13 Nov 2022 11:10
URI: https://orca.cardiff.ac.uk/id/eprint/60464

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