RGD Reference Report - 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?

General

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?
Authors:	Paul, A G van Der Zee, R Taams, L S van Eden, W
Citation:	Paul AG, etal., Int Immunol. 2000 Jul;12(7):1041-50.
RGD ID:	12910542
Pubmed:	PMID:10882416 (View Abstract at PubMed)
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.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
Experimental Arthritis		ISO	Hspd1 (Rattus norvegicus)	12910542; 12910542		RGD
Experimental Arthritis		IDA		12910542		RGD

Objects Annotated

Genes (Rattus norvegicus)

Hspd1 (heat shock protein family D (Hsp60) member 1)

Genes (Mus musculus)

Hspd1 (heat shock protein 1 (chaperonin))

Genes (Homo sapiens)

HSPD1 (heat shock protein family D (Hsp60) member 1)

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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?