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. 1998 May;94(1):64–71. doi: 10.1046/j.1365-2567.1998.00475.x

Constitutive and regulated expression of the class IB molecule Qa-1 in pancreatic beta cells.

T Chun 1, C J Aldrich 1, M E Baldeón 1, L V Kawczynski 1, M J Soloski 1, H R Gaskins 1
PMCID: PMC1364332  PMID: 9708188

Abstract

Enhanced major histocompatibility complex (MHC) class I expression is a prominent early feature of pancreatic beta-cell pathology in autoimmune diabetes. The number and nature of class I MHC loci expressed by beta cells are generally undefined and potentially critical to the onset and progression of insulitis. Mounting evidence indicates that the non-classical MHC class IB molecule Qa-1, encoded by H2-T23, is capable of presenting antigens to alpha beta and gamma delta T cells and that lymphocytes restricted to Qa-1 may contribute immunoregulatory functions. We compared the expression of Qa-1 and MHC class IA in a beta-cell line (beta TC6-F7) before and after treatment with the insulitic cytokine interferon-gamma (IFN-gamma). Similar to MHC class IA, Qa-1 was expressed constitutively at a low level in beta TC6-F7 cells, with both T23b mRNA and cell surface Qa-1b being up-regulated following 24-hr treatment with mouse IFN-gamma. Based on binding characteristics established for the predominant Qa-1-binding peptide, Qa-1 determinant modifier (Qdm), we also examined the possibility that Qa-1 binding peptides may be encoded in the preproinsulin leader sequence. One nonarmeric peptide (Ins II: ALWMRFLPL) derived from the preproinsulin II leader sequence was recognized by a Qa-1b-specific cytotoxic T-lymphocyte (CTL) clone. Specific binding of Ins II to Qa-1b was confirmed by a CTL peptide-blocking assay. Demonstration of IFN-gamma-regulated Qa-1 expression in beta cells and identification of a Qa-1-binding peptide in the preproinsulin leader sequence invoke further consideration of possible roles of Qa-1 in the progression of islet inflammation.

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Selected References

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