Structural analysis of mycobacterial and murine hsp60 epitopes in complex with the class I MHC molecule H-2D b

Abstract

The decameric peptide SALQNAASIA from the Mycobacterium bovis heat shock protein (hsp) 60 is recognized by the murine T-cell receptor UZ-3-4 in complex with the murine class I major histocompatibility complex molecule H-2D b. This T-cell receptor cross-reacts with the H-2D b-bound non-homologous decameric peptide KDIGNIISDA from the murine hsp60, but does not recognize the nonameric mycobacterial peptide SALQNAASI. Cross-recognition of the KDIGNIISDA/H-2D b complex induces autoimmune pathology in immunodeficient mice. We solved the X-ray crystal structure of the SALQNAASIA/H-2D b complex at 3.0 Å resolution, and we modelled the KDIGNIISDA and SALQNAASI peptides in the H-2D b binding site. The structural analysis of the H-2D b-bound hsp60 epitopes offers insight into T-cell receptor cross-reactivity.