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?
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.
Paul
A G
AG
Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands.
van Der Zee
R
R
Taams
L S
LS
van Eden
W
W
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D000943:Antigens, Differentiation / Q000378:metabolism; D001169:Arthritis, Experimental / Q000209:etiology*; D051940:B7-2 Antigen; D001426:Bacterial Proteins / Q000276:immunology*; D060908:CTLA-4 Antigen; D018834:Chaperonin 60 / Q000276:immunology*; D018796:Immunoconjugates; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D009161:Mycobacterium / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D013601:T-Lymphocytes / Q000502:physiology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D051940:B7-2 Antigen; D001426:Bacterial Proteins; D060908:CTLA-4 Antigen; C497966:Cd86 protein, rat; D018834:Chaperonin 60; C556708:Ctla4 protein, rat; D018796:Immunoconjugates; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4; D000069594:Abatacept; D007371:Interferon-gamma