A T cell receptor flattens a bulged antigenic peptide presented by a major histocompatibility complex class I molecule.
Plasticity of the T cell receptor (TCR) is a hallmark of major histocompatibility complex (MHC)-restricted T cell recognition. However, it is unclear whether interactions of TCR and peptide-MHC class I (pMHCI) always conform to this paradigm. Here we describe the structure of a TCR, ELS4, in its non-ligand-bound form and in complex with a prominent 'bulged' Epstein-Barr virus peptide bound to HLA-B(*)3501. This complex was atypical of previously characterized TCR-pMHCI interactions in that a rigid face of the TCR crumpled the bulged antigenic determinant. This peptide 'bulldozing' created a more featureless pMHCI determinant, allowing the TCR to maximize MHC class I contacts essential for MHC class I restriction of TCR recognition. Our findings represent a mechanism of antigen recognition whereby the plasticity of the T cell response is dictated mainly by adjustments in the MHC-bound peptide.
Tynan
Fleur E
FE
Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.
Reid
Hugh H
HH
Kjer-Nielsen
Lars
L
Miles
John J
JJ
Wilce
Matthew C J
MC
Kostenko
Lyudmila
L
Borg
Natalie A
NA
Williamson
Nicholas A
NA
Beddoe
Travis
T
Purcell
Anthony W
AW
Burrows
Scott R
SR
McCluskey
James
J
Rossjohn
Jamie
J
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000956:Antigens, Viral / Q000737:chemistry* / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry* / Q000276:immunology; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D020836:Protein Structure, Quaternary; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000276:immunology
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell