Constitutive and regulated expression of the class IB molecule Qa-1 in pancreatic beta cells.
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.
Chun
T
T
Department of Animal Sciences, University of Illinois at Urbana-Champaign 61801, USA.
Aldrich
C J
CJ
Baldeón
M E
ME
Kawczynski
L V
LV
Soloski
M J
MJ
Gaskins
H R
HR
D000818:Animals; D017951:Antigen Presentation; D015153:Blotting, Western; D003602:Cytotoxicity, Immunologic; D006183:H-2 Antigens / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007328:Insulin; D007371:Interferon-gamma / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology; D016133:Polymerase Chain Reaction; D011384:Proinsulin / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; C032907:Q surface antigens; D011994:Recombinant Proteins; C013737:preproinsulin; D007371:Interferon-gamma; D011384:Proinsulin