6EQB

HLA class I histocompatibility antigen

Summary for 6EQB

• Entry DOI: 10.2210/pdb6eqb/pdb
• Related: 3HG1
• Descriptor: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, ALA-ALA-GLY-ILE-GLY-ILE-LEU-THR-VAL, ... (9 entities in total)
• Functional Keywords: melanoma, immune system, vaccine, tcr, mhc, 3d structure
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 94761.02

Authors

Rizkallah, P.J.,Cole, D.K. (deposition date: 2017-10-12, release date: 2018-10-10, Last modification date: 2024-01-17)

Primary citation

Madura, F.,Rizkallah, P.J.,Legut, M.,Holland, C.J.,Fuller, A.,Bulek, A.,Schauenburg, A.J.,Trimby, A.,Hopkins, J.R.,Wells, S.A.,Godkin, A.,Miles, J.J.,Sami, M.,Li, Y.,Liddy, N.,Jakobsen, B.K.,Loveridge, E.J.,Cole, D.K.,Sewell, A.K.
TCR-induced alteration of primary MHC peptide anchor residue.
Eur.J.Immunol., 49:1052-1066, 2019

PubMed Abstract: The HLA-A*02:01-restricted decapeptide EAAGIGILTV, derived from melanoma antigen recognized by T-cells-1 (MART-1) protein, represents one of the best-studied tumor associated T-cell epitopes, but clinical results targeting this peptide have been disappointing. This limitation may reflect the dominance of the nonapeptide, AAGIGILTV, at the melanoma cell surface. The decapeptide and nonapeptide are presented in distinct conformations by HLA-A*02:01 and TCRs from clinically relevant T-cell clones recognize the nonapeptide poorly. Here, we studied the MEL5 TCR that potently recognizes the nonapeptide. The structure of the MEL5-HLA-A*02:01-AAGIGILTV complex revealed an induced fit mechanism of antigen recognition involving altered peptide-MHC anchoring. This "flexing" at the TCR-peptide-MHC interface to accommodate the peptide antigen explains previously observed incongruences in this well-studied system and has important implications for future therapeutic approaches. Finally, this study expands upon the mechanisms by which molecular plasticity can influence antigen recognition by T cells.

PubMed: 31091334
DOI: 10.1002/eji.201948085

Experimental method

X-RAY DIFFRACTION (2.81 Å)