Brown M G, Driscoll J, Monaco J J
Department of Microbiology and Immunology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0678.
Nature. 1991 Sep 26;353(6342):355-7. doi: 10.1038/353355a0.
Major histocompatibility complex (MHC) class I molecules associate with peptides derived from endogenously synthesized antigens. Cytotoxic T-lymphocytes can thus scan class I molecules and bound peptide on the surface of cells for foreign antigenic determinants. Recent evidence demonstrates that the products of trans-acting, non-class I genes in the class II region of the MHC are required in the class I antigen-processing pathway. There are genes (called HAM1 and HAM2 in the mouse) in this region that encode proteins postulated to be involved in the transport of peptide fragments into the endoplasmic reticulum for association with newly synthesized class I molecules. But, the mechanism by which such peptide fragments are produced remains a mystery. At least two genes encoding subunits of the low-molecular mass polypeptide (LMP) complex are tightly linked to the HAM1 and HAM2 genes. We show that the LMP complex is closely related to the proteasome (multicatalytic proteinase complex), an intracellular protein complex that has multiple proteolytic activities. We speculate that the LMP complex may have a role in MHC class I antigen processing, and therefore that the MHC contains a cluster of genes required for distinct functions in the antigen processing pathway.
主要组织相容性复合体（MHC）I类分子与内源性合成抗原衍生的肽段相结合。细胞毒性T淋巴细胞因此能够扫描细胞表面的I类分子及与之结合的肽段，以寻找外来抗原决定簇。最近的证据表明，MHC II类区域中反式作用的非I类基因产物在I类抗原加工途径中是必需的。该区域存在一些基因（在小鼠中称为HAM1和HAM2），它们编码的蛋白质被推测参与肽片段向内质网的转运，以便与新合成的I类分子相结合。但是，此类肽片段的产生机制仍是个谜。至少有两个编码低分子量多肽（LMP）复合体亚基的基因与HAM1和HAM2基因紧密连锁。我们发现LMP复合体与蛋白酶体（多催化蛋白酶复合体）密切相关，蛋白酶体是一种具有多种蛋白水解活性的细胞内蛋白复合体。我们推测LMP复合体可能在MHC I类抗原加工中发挥作用，因此MHC含有一组在抗原加工途径中具有不同功能所需的基因。
