Premium
How much can a T‐cell antigen receptor adapt to structurally distinct antigenic peptides?
Author(s) -
Mazza Catherine,
AuphanAnezin Nathalie,
Gregoire Claude,
Guimezanes Annick,
Kellenberger Christine,
Roussel Alain,
Kearney Alice,
van der Merwe P Anton,
SchmittVerhulst AnneMarie,
Malissen Bernard
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601605
Subject(s) - t cell receptor , biology , major histocompatibility complex , degeneracy (biology) , antigen , mhc restriction , t cell , microbiology and biotechnology , effector , epitope , genetics , immune system
Binding degeneracy is thought to constitute a fundamental property of the T‐cell antigen receptor (TCR), yet its structural basis is poorly understood. We determined the crystal structure of a complex involving the BM3.3 TCR and a peptide (pBM8) bound to the H‐2K bm8 major histocompatibility complex (MHC) molecule, and compared it with the structures of the BM3.3 TCR bound to H‐2K b molecules loaded with two peptides that had a minimal level of primary sequence identity with pBM8. Our findings provide a refined structural view of the basis of BM3.3 TCR cross‐reactivity and a structural explanation for the long‐standing paradox that a TCR antigen‐binding site can be both specific and degenerate. We also measured the thermodynamic features and biological penalties that incurred during cross‐recognition. Our data illustrate the difficulty for a given TCR in adapting to distinct peptide‐MHC surfaces while still maintaining affinities that result in functional in vivo responses. Therefore, when induction of protective effector T cells is used as the ultimate criteria for adaptive immunity, TCRs are probably much less degenerate than initially assumed.