Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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 agents1. For example, a subset of patients with a history of Salmonella infection develop reactive arthritis2,3,4,5,6. 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 disease7,8. Models proposed to account for the link between infection and autoimmunity include inflammation-induced presentation of cryptic self-epitopes, antigen persistence and molecular mimicry1. Several studies support molecular mimicry as a mechanism for the involvement of class II epitopes in infectious disease-induced self-reactivity9,10,11,12. 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.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Identification of Salmonella-derived epitopes presented by Qa-1b.
Figure 2: Recognition of bacterial GroEL192-200 and self homolog hsp60216-224 by Qa-1b-restricted CTLs.
Figure 3: Qa-1b-restricted CTLs recognize uninfected stressed macrophages.


  1. Rose, N.R. The role of infection in the pathogenesis of autoimmune disease. Sem. Immunol. 10, 5–13 (1998)

    CAS  Article  Google Scholar 

  2. Maki-Ikola, O. Reactive arthritis after unusual Salmonella infections. Lancet 336, 1387 (1990).

    CAS  Article  Google Scholar 

  3. Granfors, K. et al. Salmonella lipopolysaccharide in synovial cells from patients with reactive arthritis. Lancet 335, 685–688 (1990).

    CAS  Article  Google Scholar 

  4. Yu, D. & Inman, R. Infectious agents and other nongenetic immunologic factors in spondyloarthropathies. Curr. Opin. Rheumatol. 3, 581–585 (1991).

    CAS  Article  Google Scholar 

  5. Taggart, A.J. & Bell, A.L. Reactive arthritis: a further consequence of the increase in salmonella infections Br. Med. J. 298, 674 (1989).

    CAS  Article  Google Scholar 

  6. Kondowe, G.B., Bell, A.L., Middleton, D. & Taggart, A.J. An outbreak of Salmonella reactive arthritis in Northern Ireland. Ir. J. Med. Sci. 158, 274–277 (1989).

    CAS  Article  Google Scholar 

  7. Hermann, E. T cells in reactive arthritis. APMIS 101, 177–186 (1993).

    CAS  Article  Google Scholar 

  8. Sieper, J. & Braun, J. Pathogenesis of spondylarthropathies. Persistent bacterial antigen, autoimmunity, or both? Arthritis Rheum. 38, 1547–1554 (1995).

    CAS  Article  Google Scholar 

  9. Hemmer, B. et al. Identification of high potency microbial and self ligands for a human autoreactive class II-restricted T cell clone. J. Exp. Med. 185, 1651–1659 (1997).

    CAS  Article  Google Scholar 

  10. Wucherpfennig, K.W. & Strominger, J.L. Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell 80, 695–705 (1995).

    CAS  Article  Google Scholar 

  11. Gross, D.M., et al. Identification of LFA-1 as a candidate autoantigen in treatment-resistant Lyme arthritis. Science 281, 703–706 (1998).

    CAS  Article  Google Scholar 

  12. Zhao, Z.S., Granucci, F., Yeh, L., Schaffer, P.A. & Cantor, H. Molecular mimicry by herpes simplex virus-type 1: autoimmune disease after viral infection. Science 279, 1344–1347 (1998).

    CAS  Article  Google Scholar 

  13. Lo, W.-F., Ong, H., Metcalf, E.S. & Soloski, M.J. Cytotoxic T cell responses to Gram-negative intracellular bacterial pathogens: A role for CD8+ T cells in immunity to Salmonella infection and involvement of class Ib molecules. J. Immunol. 162, 5398–5406 (1999).

    CAS  Google Scholar 

  14. Aldrich, C.J. et al. Identification of a Tap-dependent leader peptide recognized by alloreactive T Cells specific for a class Ib antigen. Cell 79, 649–658 (1994).

    CAS  Article  Google Scholar 

  15. Kurepa, Z. & Forman, J. Peptide binding to the class Ib molecule, Qa-1b. J. Immunol. 158, 3244–3251 (1997).

    CAS  Google Scholar 

  16. Imani, F. & Soloski, M.J. Heat shock proteins can regulate expression of the Tla region-encoded class Ib molecule Qa-1. Proc. Natl. Acad. Sci. USA 88, 10475–10479 (1991).

    CAS  Article  Google Scholar 

  17. Koga, T. et al. T cells against a bacterial heat shock protein recognize stressed macrophages. Science 245, 1112–1115 (1989).

    CAS  Article  Google Scholar 

  18. Lee, N., Goodlett, D.R., Ishitani, A., Marquardt, H. & Geraghty, D.E. HLA-E surface expression depends on binding of TAP-dependent peptides derived from certain HLA class I signal sequences. J. Immunol. 160, 4951–4960 (1998).

    CAS  Google Scholar 

  19. Braud, V.M. et al. HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature 391, 795–799 (1998).

    CAS  Article  Google Scholar 

  20. Zugel, U. & Kaufmann, S.H.E. Activation of CD8 T cells with specificity for mycobacterial heat shock protein 60 in Mycobacterium Bovis Bacillus Calmette-Guerin-vaccinated mice. Infect. Immun. 65, 3947–3950 (1997).

    CAS  Google Scholar 

  21. Hermann, E. et al. MHC-unrestricted recognition of bacteria-infected target cells by human CD8+ cytotoxic T lymphocytes. Cell. Immunol. 143, 253–260 (1992).

    CAS  Article  Google Scholar 

  22. Life, P.F., Bassey, E.O.E. & Gaston, J.S.H. T-cell recognition of bacterial heat shock proteins in inflammatory arthritis. Immunol. Rev. 121, 113–135 (1991).

    CAS  Article  Google Scholar 

  23. Russmann, H. et al. Delivery of epitopes by the Salmonella type III secretion system for vaccine development. Science 281, 565–568 (1998).

    CAS  Article  Google Scholar 

  24. DeCloux, A., Woods, A.S., Cotter, R.J., Soloski, M.J. & Forman, J.F. Dominance of a single peptide bound to the class Ib molecule Qa-1b. J. Immunol. 158, 2193–2191 (1997).

    Google Scholar 

  25. Coico, R. Current Protocols in Immunology (John Wiley and Sons, New York, 1994).

    Google Scholar 

Download references


We thank R. Siliciano, D. Pardoll, M. Schlissel and A. Rosen for their critical reading of the manuscript and suggestions. This work was supported by National Institutes of Health grants RO1AI20922 and RO1AI42287 and by an Award from the Maryland Chapter of the National Arthritis Foundation (M.J.S.) and by National Institutes of Health grants RO1AI32951 and USUHS R07FE (E.S.M.) and RO1GM54882 (R.J.C.).

Author information

Authors and Affiliations


Corresponding author

Correspondence to Mark J. Soloski.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Lo, WF., Woods, A., DeCloux, A. et al. Molecular mimicry mediated by MHC class Ib molecules after infection with Gram-negative pathogens. Nat Med 6, 215–218 (2000).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing