Inflammation-associated nitrotyrosination affects TCR recognition through reduced stability and alteration of the molecular surface of the MHC complex.

ABSTRACT: Nitrotyrosination of proteins, a hallmark of inflammation, may result in the production of MHC-restricted neoantigens that can be recognized by T cells and bypass the constraints of immunological self-tolerance. Here we biochemically and structurally assessed how nitrotyrosination of the lymphocytic choriomeningitis virus (LCMV)-associated immunodominant MHC class I-restricted epitopes gp33 and gp34 alters T cell recognition in the context of both H-2D(b) and H-2K(b). Comparative analysis of the crystal structures of H-2K(b)/gp34 and H-2K(b)/NY-gp34 demonstrated that nitrotyrosination of p3Y in gp34 abrogates a hydrogen bond interaction formed with the H-2K(b) residue E152. As a consequence the conformation of the TCR-interacting E152 was profoundly altered in H-2K(b)/NY-gp34 when compared

SUBMITTER: Madhurantakam C 

PROVIDER: S-EPMC3303804 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature