Naturally presented HLA class I–restricted epitopes from the neurotrophic factor S100-β are targets of the autoimmune response in type 1 diabetes

What is it about?

In the present study we have evaluated the autoimmune response to a novel antigen in type 1 or insulin-dependent diabetes. This novel antigen is a protein present in cells surrounding the pancreatic islets called peri-insular Schwann (pSC) cells. Those pSC cells express antigens not shared with the pancreatic insulin-producing beta cells such as the neurothropic factor S100beta. We have identified segments derived from S100beta, called peptides, that are presented to cytotoxic T lymphocytes (CTLs) and capable to activate those cells. These peptides are recognized by CTLs obtained from human type 1 diabetes (T1D) patients. Moreover, the same peptides are also capable of activating CTLs obtained from a mouse model of T1D expressing a human histocompatibility molecule (HLA) implicated in the development of T1D, the NOD mice expressing the HLA molecule A2.1. Interestingly, when those peptides were used to prevent disease development in those mice, an acceleration rather than protection from T1D was observed. Immunotherapy using those S100beta-derived peptides activated CTLs to destroy those pSC cells accelerating diabetes develpment. Present results reinforce the idea that diabetes development include the targeting of pSC cells. The use of peptides derived from S100beta and recognized by CTLs require a careful analysis regarding doses and mode of administration to induce tolerance and prevent T1D development.

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