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

T. Chun, Carla Aldrich, M. E. Baldeón, L. V. Kawczynski, M. J. Soloski, H. R. Gaskins

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Abstract

Enhanced major histocompatibility complex (MHC) class I expression is a prominent early feature of pancreatic β-cell pathology in autoimmune diabetes. The number and nature of class I MHC loci expressed by β 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 αβ and γδ 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 β-cell line (βTC6-F7) before and after treatment with the insulitic cytokine interferon-γ (IFN-γ). Similar to MHC class IA, Qa-1 was expressed constitutively at a low level in βTC6-F7 cells, with both T23b mRNA and cell surface Qa-1b being up-regulated following 24-hr treatment with mouse IFN-γ. 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 nonameric 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-γ-regulated Qa-1 expression in β 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.

Original languageEnglish
Pages (from-to)64-71
Number of pages8
JournalImmunology
Volume94
Issue number1
DOIs
StatePublished - 1998

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Major Histocompatibility Complex
Peptides
Interferons
Cytotoxic T-Lymphocytes
Type 1 Diabetes Mellitus
Clone Cells
Lymphocytes
Pathology
Cytokines
Inflammation
T-Lymphocytes
Antigens
Cell Line
Messenger RNA
preproinsulin

ASJC Scopus subject areas

  • Immunology

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Constitutive and regulated expression of the class IB molecule Qa-1 in pancreatic β cells. / Chun, T.; Aldrich, Carla; Baldeón, M. E.; Kawczynski, L. V.; Soloski, M. J.; Gaskins, H. R.

In: Immunology, Vol. 94, No. 1, 1998, p. 64-71.

Research output: Contribution to journalArticle

Chun, T. ; Aldrich, Carla ; Baldeón, M. E. ; Kawczynski, L. V. ; Soloski, M. J. ; Gaskins, H. R. / Constitutive and regulated expression of the class IB molecule Qa-1 in pancreatic β cells. In: Immunology. 1998 ; Vol. 94, No. 1. pp. 64-71.
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