Novel mutants define genes required for the expression of human histocompatibility leukocyte antigen DM: evidence for loci on human chromosome 6p.
Novel mutants define genes required for the expression of human histocompatibility leukocyte antigen DM: evidence for loci on human chromosome 6p.
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新型突变体定义了人类组织相容性白细胞抗原DM所需的基因：对人类6p染色体的基因座的证据。
DOI：
10.1084/jem.186.9.1469
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发表时间：
1997-11-03
影响因子：
15.3
通讯作者：
Pious, D
中科院分区：
文献类型：
--
作者：
Fling, SP;Rak, J;Muczynski, KA;Arp, B;Pious, D
我们和其他人已经证明，主要组织相容性复合体II类分子与同源多肽在细胞内组装时，需要人类白细胞抗原-DM基因座的产物来呈递抗原。HL A-DM异源二聚体介导不变链(II)衍生的II类相关II肽(CLIP)从II类分子中解离，并促进II类分子负载抗原肽。在这里，我们描述了新的APC突变体，这些突变体在形成II类多肽复合体方面存在缺陷。这些突变体表达构象改变的II类分子，并且这些II类分子中异常高的比例与II衍生的CLIP相关。这一表型与DM缺失突变体相似。然而，我们发现这些新突变体中的两个缺陷并不映射到DM基因。然而，我们的证据表明，这些突变体中的抗原处理缺陷表型是由于DM表达不足所致。因此，这些突变体似乎定义了基因，其中突变对传统的II类分子和DM分子的表达具有不同的影响。我们的数据与这些因素在人类染色体6p上的定位最为一致。以往的数据表明，DM和II类基因的表达是协同调控的。这些结果表明，DM和II类抗原也可以受到不同的调节，这种不同的调节对II类限制性抗原的处理有显著的影响。
We and others have shown that the products of the HLA-DM locus are required for the intracellular assembly of major histocompatibility complex class II molecules with cognate peptides for antigen presentation. HLA-DM heterodimers mediate the dissociation of invariant chain (Ii)-derived class II–associated Ii peptides (CLIP) from class II molecules and facilitate the loading of class II molecules with antigenic peptides. Here we describe novel APC mutants with defects in the formation of class II–peptide complexes. These mutants express class II molecules which are conformationally altered, and an aberrantly high percentage of these class II molecules are associated with Ii-derived CLIP. This phenotype resembles that of DM null mutants. However, we show that the defects in two of these new mutants do not map to the DM locus. Nevertheless, our evidence suggests that the antigen processing defective phenotype in these mutants results from deficient DM expression. These mutants thus appear to define genes in which mutations have differential effects on the expression of conventional class II molecules and DM molecules. Our data are most consistent with these factors mapping to human chromosome 6p. Previous data have suggested that the expression of DM and class II genes are coordinately regulated. The results reported here suggest that DM and class II can also be differentially regulated, and that this differential regulation has significant effects on class II–restricted antigen processing.
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影响因子：
56.9
作者：
KARLSSON, L;PELERAUX, A;PETERSON, PA
通讯作者：
PETERSON, PA
影响因子：
64.5
作者：
BAKKE, O;DOBBERSTEIN, B
通讯作者：
DOBBERSTEIN, B
影响因子：
56.9
作者：
HUNT, DF;MICHEL, H;SETTE, A
通讯作者：
SETTE, A
使用小鼠单克隆抗体对DR3特异的小分子量（β）亚基的HLA-DR同型决定因素的直接证明。
影响因子：
15.3
作者：
Johnson, J P;Meo, T;Riethmuller, G;Schendel, D J;Wank, R
通讯作者：
Wank, R
影响因子：
2.9
作者：
GLISIN, V;CRKVENJAKOV, R;BYUS, C
通讯作者：
BYUS, C