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

The development of many autoimmune diseases has been etiologically linked t o exposure to infectious agents(1). For example, a subset of patients with a history of Salmonella infection develop reactive arthritis(2-6). The pers istence of bacterial antigen in arthritic tissue and the isolation of Salmo nella or Yersinia reactive CD8(+) T cells from the joints of patients with reactive arthritis support the etiological link between Gram-negative bacte rial infection and autoimmune disease(7,8). Models proposed to account for the link between infection and autoimmunity include inflammation-induced pr esentation of cryptic self-epitopes, antigen persistence and molecular mimi cry(1). Several studies support molecular mimicry as a mechanism for the in volvement of class II epitopes in infectious disease-induced self-reactivit y(9-12). Here, we have identified an immunodominant epitope derived from th e S. typhimurium GroEL molecule. This epitope is presented by the mouse H2- T23-encoded class Ib molecule Qa-l and was recognized by CD8(+) cytotoxic T lymphocytes induced after natural infection. S. typhimurium-stimulated cyt otoxic T lymphocytes recognizing the GroEL epitope cross-reacted with a pep tide derived from mouse heat shock protein 60 and recognized stressed macro phages. Our results indicate involvement of MHC class ib molecules in infec tion-induced autoimmune recognition and indicate a mechanism for the etiolo gical link between Gram-negative bacterial infection and autoimmunity.