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.