Major histocompatibility complex class II-restricted presentation of an internally synthesized antigen displays cell-type variability and segregates from the exogenous class II and endogenous class I presentation pathways.
Major histocompatibility complex class II-restricted presentation of an internally synthesized antigen displays cell-type variability and segregates from the exogenous class II and endogenous class I presentation pathways.
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DOI：
10.1084/jem.178.1.73
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发表时间：
1993-07-01
期刊：
影响因子：
--
通讯作者：
Sant AJ
中科院分区：
文献类型：
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作者：
Loss GE Jr;Elias CG;Fields PE;Ribaudo RK;McKisic M;Sant AJ
虽然报道的主要组织相容性复合体（MHC）II类分子的内源性抗原（Ag）呈递的例子有所增加，但这一过程的机制仍然不清楚。在这篇文章中，我们描述了一个实验系统，旨在研究内部Ag的II类呈现机制。我们的靶肽是从由多种有核细胞（MHC I类，H-2Ld）组成性表达的跨膜蛋白加工的，在体内由MHC II类分子天然展示，并且由II类限制性的CD 4 + T细胞杂交瘤识别。我们的研究结果表明，介绍的Ld目标银是独立的质膜表达，可能不涉及内体蛋白水解，因此可能不同于经典定义的II类介绍途径。此外，Ld呈递不需要功能性TAP-1复合物，不被不变链阻断，并且不能利用H- 2Ld的细胞质形式的观察结果表明，经典的I类途径不参与该呈递事件。最后，我们的数据表明，不同的辅因子参与MHC II类呈递外源性和内源性Ag，不同的Ag呈递细胞，如B，T和胰岛细胞，可能差异表达这两个II类途径的Ag呈递。
Although reported examples of endogenous antigen (Ag) presentation by major histocompatibility complex (MHC) class II molecules have increased, the mechanisms governing this process remain poorly defined. In this communication, we describe an experimental system designed to examine the mechanisms governing class II presentation of internal Ag. Our target peptide is processed from a transmembrane protein constitutively expressed by a variety of nucleated cells (MHC class I, H-2Ld), is naturally displayed by MHC class II molecules in vivo, and is recognized by a class II-restricted, CD4+ T cell hybridoma. Our results indicate that presentation of the Ld target Ag is independent of its plasma membrane expression, may not involve endosomal proteolysis, and thus may be distinct from the classically defined class II presentation pathway. In addition, the observations that Ld presentation does not require a functional TAP-1 complex, is not blocked by invariant chain, and cannot utilize cytoplasmic forms of H- 2Ld, suggest that a classical class I pathway is not involved in this presentation event. Finally, our data suggest that different cofactors participate in MHC class II presentation of exogenous and endogenous Ag, and that disparate Ag presenting cells, such as B, T, and pancreatic islet cells, may differentially express these two class II pathways of Ag presentation.