We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
TCR‐induced alteration of primary MHC peptide anchor residue.
- Authors
Madura, Florian; Rizkallah, Pierre J.; Legut, Mateusz; Holland, Christopher J.; Fuller, Anna; Bulek, Anna; Schauenburg, Andrea J.; Trimby, Andrew; Hopkins, Jade R.; Wells, Stephen A.; Godkin, Andrew; Miles, John J.; Sami, Malkit; Li, Yi; Liddy, Nathaniel; Jakobsen, Bent K.; Loveridge, E. Joel; Cole, David K.; Sewell, Andrew K.
- 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.
- Subjects
IMMUNE recognition; T cell receptors; CELL membranes; T cells; SURFACE plasmon resonance; CELLULAR recognition
- Publication
European Journal of Immunology, 2019, Vol 49, Issue 7, p1052
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201948085