Treatment of NOD diabetes with a novel peptide of the hsp60 molecule induces th2-type antibodies

A peptide from the sequence of hsp60 molecule, designated p277, has been shown to be functionally involved in modulating the development of autoimmune diabetes in the NOD mouse: administration of p277 to NOD mice can arrest the diabetogenic autoimmune process, even when far advanced. Is p277 the only hsp60 peptide able to modulate the disease? We mapped T cell responses to peptides spanning the mouse hsp60 molecule and identified an immunogenic peptide, designated p12, that is also functional in arresting NOD diabetes. Although no spontaneous T cell reactivity to p12 could be detected in NOD mice, subcutaneous administration of 100 mu g of p12 in mineral oil to 10-week-old female NOD mice, similar to treatment with p277, significantly prevented progression of the disease. Administration of other immunogenic peptides was not effective. A peptide from the glutamic acid decarboxylase (GAD65) sequence, GADp35, and a peptide from the mycobacterial hsp60 molecule did not influence the development of diabetes. The effectiveness of hsp60 peptides p12 and p277 was associated with the induction of antibodies to the peptides of the IgG1 and IgG2b isotypes, antibodies which appear to be regulated by anti-inflammatory cytokines. There was a negative correlation between the amounts of antibodies induced by the hsp60 peptides and the level of blood glucose. Thus, more than one peptide of the hsp60 molecule can be used to inhibit the development of NOD diabetes, and the effect of peptide therapy arrears to be associated with the induction of specific antibody isotypes. (C) 1997 Academic Press Limited.