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

Constitutive and regulated expression of the class IB molecule Qa-1 in pancreatic beta cells.
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IB 类分子 Qa-1 在胰腺 β 细胞中的组成型和调节表达。

DOI:
10.1046/j.1365-2567.1998.00475.x
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发表时间:
1998
期刊:
影响因子:
6.4
通讯作者:
Gaskins,HR
Gaskins,HR
中科院分区:
医学2区
文献类型:
--
作者:
Chun,T;Aldrich,CJ;Baldeón,ME;Kawczynski,LV;Soloski,MJ;Gaskins,HR

文献摘要

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Enhanced major histocompatibility complex (MHC) class I expression is a prominent early feature of pancreatic β‐cell pathology in autoimm_une 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 byH2‐T23, is capable of presenting antigens to αβ and γδ T cells and that lymphocytes restricted to Qa‐1 may contribute imm_unoregulatory 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 bothT23bmRNA and cell surface Qa‐1bbeing 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‐1bwas 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.