Minimal conformational plasticity enables TCR cross-reactivity to different MHC class II heterodimers

Holland, Christopher J., Rizkallah, Pierre ORCID: https://orcid.org/0000-0002-9290-0369, Vollers, Sabrina, Calvo-Calle, J. Mauricio, Madura, Florian, Fuller, Anna, Sewell, Andrew K. ORCID: https://orcid.org/0000-0003-3194-3135, Stern, Lawrence J., Godkin, Andrew James ORCID: https://orcid.org/0000-0002-1910-7567 and Cole, David ORCID: https://orcid.org/0000-0003-0028-9396 2012. Minimal conformational plasticity enables TCR cross-reactivity to different MHC class II heterodimers. Scientific Reports 2 , 629. 10.1038/srep00629

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Abstract

Successful immunity requires that a limited pool of αβ T-cell receptors (TCRs) provide cover for a vast number of potential foreign peptide antigens presented by ‘self’ major histocompatibility complex (pMHC) molecules. Structures of unligated and ligated MHC class-I-restricted TCRs with different ligands, supplemented with biophysical analyses, have revealed a number of important mechanisms that govern TCR mediated antigen recognition. HA1.7 TCR binding to the influenza hemagglutinin antigen (HA306–318) presented by HLA-DR1 or HLA-DR4 represents an ideal system for interrogating pMHC-II antigen recognition. Accordingly, we solved the structure of the unligated HA1.7 TCR and compared it to both complex structures. Despite a relatively rigid binding mode, HA1.7 T-cells could tolerate mutations in key contact residues within the peptide epitope. Thermodynamic analysis revealed that limited plasticity and extreme favorable entropy underpinned the ability of the HA1.7 T-cell clone to cross-react with HA306–318 presented by multiple MHC-II alleles.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QR Microbiology > QR180 Immunology R Medicine > R Medicine (General)
Uncontrolled Keywords:	immunology, molecular biology, structural biology, biophysics
ISSN:	20452322
Last Modified:	06 May 2023 02:26
URI:	https://orca.cardiff.ac.uk/id/eprint/41669

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