Compensatory mechanisms allow undersized anchor-deficient class I MHC ligands to mediate pathogenic autoreactive T cell responses.

ABSTRACT: Self-reactive T cells must escape thymic negative selection to mediate pathogenic autoimmunity. In the NOD mouse model of autoimmune diabetes, several β cell-cytotoxic CD8 T cell populations are known, with the most aggressive of these represented by AI4, a T cell clone with promiscuous Ag-recognition characteristics. We identified a long-elusive β cell-specific ligand for AI4 as an unusually short H-2D(b)-binding 7-mer peptide lacking a C-terminal anchor residue and derived from the insulin A chain (InsA14-20). Crystallography reveals that compensatory mechanisms permit peptides lacking a C-terminal anchor to bind sufficiently to the MHC to enable destructive T cell responses, yet allow cognate T cells to avoid negative selection. InsA14-20 shares two solvent-exposed residues with previou

SUBMITTER: Lamont D 

PROVIDER: S-EPMC4134999 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature