International Immunology, Vol. 12, No. 7, 1041-1050,
July 2000
© 2000 Japanese Society for Immunology
A self-hsp60 peptide acts as a partial agonist inducing expression of B7-2 on mycobacterial hsp60-specific T cells: a possible mechanism for inhibitory T cell regulation of adjuvant arthritis?
Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands
1 Department of Clinical Immunology, Royal Free and University College Medical School (Royal Free Campus), London NW3 2PF, UK
Correspondence to: W. Van Eden
We previously reported that resistance to the induction of adjuvant arthritis after preimmunization with mycobacterial hsp60 was mediated by T cells recognizing a conserved epitope (M256–270) of mycobacterial hsp60. These T cells were cross-reactive with the homologous rat hsp60 peptide sequence and the natural self-epitope on stressed antigen-presenting cells. Recognition of peptide M256–265, the conserved core of peptide M256–270, was shown to be essential for the generation of self-reactive T cells. The rat homologue of peptide M256–265, peptide R256–265, differs with three conservative amino acid substitutions from the mycobacterial core peptide. Thus peptide R256–265 could act as an altered peptide ligand with the potential of inducing a different functional phenotype in M256–270-specific T cells. We now show that peptide R256–265 was recognized by M256–270-specific T cells as a partial agonist, inducing TCR down-regulation and up-regulation of activation/adhesion molecules in the absence of proliferative responses. Peptide R256–265 did not induce anergy but induced B7-2 (but not B7-1) expression on M256–270-specific T cells, as opposed to the mycobacterial peptide, which preferentially induced B7-1. These effects were more pronounced at low peptide concentrations. Therefore also in vivo at the more relevant low physiological level of expression, the self-hsp could induce such phenotype. It is discussed how this selective up-regulation of B7-2 expression on (self-hsp60) autoreactive T cells might be a way by which destructive autoimmune responses are controlled.
Keywords: anergy, autoreactivity, B7-2, IL-4, IL-10, tolerance
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