5TEZ

TCR F50 recgonizing M1-HLA-A2

Summary for 5TEZ

• Entry DOI: 10.2210/pdb5tez/pdb
• Descriptor: GLY-ILE-LEU-GLY-PHE-VAL-PHE-THR-LEU, HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, ... (6 entities in total)
• Functional Keywords: tcr flu m1-hla-a2, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 95473.13

Authors

Yang, X.,Mariuzza, R.A. (deposition date: 2016-09-23, release date: 2017-09-27, Last modification date: 2024-11-13)

Primary citation

Yang, X.,Chen, G.,Weng, N.P.,Mariuzza, R.A.
Structural basis for clonal diversity of the human T-cell response to a dominant influenza virus epitope.
J. Biol. Chem., 292:18618-18627, 2017

PubMed Abstract: Influenza A virus (IAV) causes an acute infection in humans that is normally eliminated by CD8 cytotoxic T lymphocytes. Individuals expressing the MHC class I molecule HLA-A2 produce cytotoxic T lymphocytes bearing T-cell receptors (TCRs) that recognize the immunodominant IAV epitope GILGFVFTL (GIL). Most GIL-specific TCRs utilize α/β chain pairs encoded by the TRAV27/TRBV19 gene combination to recognize this relatively featureless peptide epitope (canonical TCRs). However, ∼40% of GIL-specific TCRs express a wide variety of other TRAV/TRBV combinations (non-canonical TCRs). To investigate the structural underpinnings of this remarkable diversity, we determined the crystal structure of a non-canonical GIL-specific TCR (F50) expressing the TRAV13-1/TRBV27 gene combination bound to GIL-HLA-A2 to 1.7 Å resolution. Comparison of the F50-GIL-HLA-A2 complex with the previously published complex formed by a canonical TCR (JM22) revealed that F50 and JM22 engage GIL-HLA-A2 in markedly different orientations. These orientations are distinguished by crossing angles of TCR to peptide-MHC of 29° for F50 69° for JM22 and by a focus by F50 on the C terminus rather than the center of the MHC α1 helix for JM22. In addition, F50, unlike JM22, uses a tryptophan instead of an arginine to fill a critical notch between GIL and the HLA-A2 α2 helix. The F50-GIL-HLA-A2 complex shows that there are multiple structurally distinct solutions to recognizing an identical peptide-MHC ligand with sufficient affinity to elicit a broad anti-IAV response that protects against viral escape and T-cell clonal loss.

PubMed: 28931605
DOI: 10.1074/jbc.M117.810382

Experimental method

X-RAY DIFFRACTION (1.7 Å)