How a single T cell receptor recognizes both self and foreign MHC.
Cell
; 129(1): 135-46, 2007 Apr 06.
Article
in En
| MEDLINE
| ID: mdl-17418792
ABSTRACT
alphabeta T cell receptors (TCRs) can crossreact with both self- and foreign- major histocompatibility complex (MHC) proteins in an enigmatic phenomenon termed alloreactivity. Here we present the 2.35 A structure of the 2C TCR complexed with its foreign ligand H-2L(d)-QL9. Surprisingly, we find that this TCR utilizes a different strategy to engage the foreign pMHC in comparison to the manner in which it recognizes a self ligand H-2K(b)-dEV8. 2C engages both shared and polymorphic residues on L(d) and K(b), as well as the unrelated QL9 and dEV8 peptide antigens, in unique pair-wise contacts, resulting in greater structural complementarity with the L(d)-QL9 complex. In the structure of an engineered, high-affinity 2C TCR variant bound to H-2L(d)-QL9, the "wild-type" TCR-MHC binding orientation persists despite modified TCR-CDR3alpha interactions with peptide. Thus, a single TCR recognizes two globally similar, but distinct ligands by divergent mechanisms, indicating that receptor-ligand crossreactivity can occur in the absence of molecular mimicry.
Search on Google
Database:
MEDLINE
Main subject:
Autoantigens
/
H-2 Antigens
/
Receptors, Antigen, T-Cell, alpha-beta
/
Isoantigens
Language:
En
Journal:
Cell
Year:
2007
Type:
Article
Affiliation country:
United States