IN-VIVO AND IN-VITRO FORMATION AND DISSOCIATION OF HLA-DR COMPLEXES WITH INVARIANT CHAIN-DERIVED PEPTIDES

IN-VIVO AND IN-VITRO FORMATION AND DISSOCIATION OF HLA-DR COMPLEXES WITH INVARIANT CHAIN-DERIVED PEPTIDES
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DOI:
10.1016/s1074-7613(94)80018-9
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发表时间:
1994-12-01
期刊:
影响因子:
32.4
通讯作者:
CRESSWELL, P
CRESSWELL, P
中科院分区:
医学1区
文献类型:
--
作者:
AVVA, RR;CRESSWELL, P

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与II类相关的不变性链肽(CLIP)相关的HLA-DR分子在体内作为II类成熟的中间体产生。这种复合物可以在体外通过蛋白水解消化DR α β I复合物而产生,这表明CLIP是在I链降解后仍与II类分子相关的残留片段。在体外,根据等位基因的不同,CLIP与DR - β二聚体的解离速率不同,低pH值和含有8-10个碳未支链烃的洗涤剂,或伯脂肪胺或羧酸都能促进CLIP的解离。DR α - β - CLIP复合物在HLA-DM阴性抗原加工突变细胞中的积累表明,依赖于HLA-DM表达的功能类似机制催化体内CLIP解离并产生正常的ii类肽复合物。
HLA-DR molecules associated with class II-associated invariant chain peptides (CLIP) are generated in vivo as an intermediate in class II maturation. Such complexes can be produced in vitro by proteolytic digestion of DR alpha beta I complexes, suggesting that CLIP is a residual fragment that remains associated with class II molecules following I chain degradation. In vitro, CLIP dissociation from DR alpha beta dimers occurs at different rates depending on the allele, and is facilitated by low pH and by detergents containing 8-10 carbon unbranched hydrocarbons, or by primary aliphatic amines or carboxylic acids. The accumulation of DR alpha beta CLIP complexes in HLA-DM-negative antigen-processing mutant cells argues that a functionally similar mechanism, dependent on HLA-DM expression, catalyzes in vivo CLIP dissociation and generation of normal class II-peptide complexes.