Molecular mimicry mediated by MHC class Ib molecules after infection with Gram-negative pathogens

The development of many autoimmune diseases has been etiologically linked to exposure to infectious agents 1 . For example, a subset of patients with a history of Salmonella infection develop reactive arthritis 2 , 3 , 4 , 5 , 6 . The persistence of bacterial antigen in arthritic tissue and the isolation of Salmonella or Yersinia reactive CD8 + T cells from the joints of patients with reactive arthritis support the etiological link between Gram-negative bacterial infection and autoimmune disease 7 , 8 . Models proposed to account for the link between infection and autoimmunity include inflammation-induced presentation of cryptic self-epitopes, antigen persistence and molecular mimicry 1 . Several studies support molecular mimicry as a mechanism for the involvement of class II epitopes in infectious disease-induced self-reactivity 9 , 10 , 11 , 12 . Here, we have identified an immunodominant epitope derived from the S. typhimurium GroEL molecule. This epitope is presented by the mouse H2-T23-encoded class Ib molecule Qa-1 and was recognized by CD8 + cytotoxic T lymphocytes induced after natural infection. S. typhimurium -stimulated cytotoxic T lymphocytes recognizing the GroEL epitope cross-reacted with a peptide derived from mouse heat shock protein 60 and recognized stressed macrophages. Our results indicate involvement of MHC class Ib molecules in infection-induced autoimmune recognition and indicate a mechanism for the etiological link between Gram-negative bacterial infection and autoimmunity.