Deverson E V, Gow I R, Coadwell W J, Monaco J J, Butcher G W, Howard J C
Department of Immunology, Cambridge Research Station, UK.
Nature. 1990;348(6303):738-41. doi: 10.1038/348738a0.
The T-cell immune response is directed against antigenic peptide fragments generated in intracellular compartments, the cytosol or the endocytic system. Peptides derived from cytosolic proteins, usually of biosynthetic origin, are presented efficiently to T-cell receptors by major histocompatibility complex (MHC) class I molecules, with which they assemble, probably in the endoplasmic reticulum (ER). In the absence of recognizable N-terminal signal sequences, such cytosolic peptides must be translocated across the ER membrane by a novel mechanism. Genes apparently involved in the normal assembly and transport of class I molecules may themselves be encoded in the MHC. Here we show that one of these, the rat cim gene, maps to a highly polymorphic part of the MHC class II region encoding two novel members of the family of transmembrane transporters related to multidrug resistance. Other members of this family of transporter proteins are known to be capable of transporting proteins and peptides across membranes independently of the classical secretory pathway. Such molecules are credible candidates for peptide pumps that move fragments of antigenic proteins from the cytosol into the ER.
T细胞免疫反应针对的是细胞内区室、胞质溶胶或内吞系统中产生的抗原肽片段。源自胞质蛋白（通常为生物合成来源）的肽，通过主要组织相容性复合体（MHC）I类分子有效地呈递给T细胞受体，它们可能在内质网（ER）中与之组装。在没有可识别的N端信号序列的情况下，此类胞质肽必须通过一种新机制转运穿过ER膜。显然参与I类分子正常组装和运输的基因本身可能由MHC编码。我们在此表明，其中一个基因，即大鼠cim基因，定位于MHC II类区域的一个高度多态性部分，该区域编码与多药耐药相关的跨膜转运蛋白家族的两个新成员。已知该转运蛋白家族的其他成员能够独立于经典分泌途径跨膜转运蛋白质和肽。此类分子是将抗原蛋白片段从胞质溶胶转运到ER中的肽泵的可信候选者。
