Quality control of MHC class II associated peptides by HLA-DM/H2-M

For many years the crucial components involved in MHC class II mediated antigen presentation have been thought to be known: polymorphic MHC class II molecules, the monomorphic invariant chain (li) and a set of conventional proteases that cleave antigenic proteins thereby generating ligands able to associate with MHC class II molecules. However, in 1994 it was found that without an additional molecule, HLA-DM (DM), efficient presentation of protein antigens cannot be achieved. Biochemical studies showed that DM acts as a molecular chaperone protecting empty MHC class II molecules from functional inactivation. In addition, it serves as a peptide editor: DM catalyzes not only the release of the invariant chain remnant CLIP, but of all sorts of low-stability peptides, and simultaneously favors binding of high-stability peptides. Through this quality control of peptide loading, DM enables APCs to optimize MHC restriction and to display their antigenic peptide cargo on the surface for prolonged periods of time to be scrutinized by T cells.     

三氯乙烯药疹样皮炎与HLA-DMA及HLA-DMB的关系

目的 根据人白细胞抗原（HLA）-DMA及HLA-DMB在三氯乙烯药疹样皮炎（DMLT）和正常对照分布情况,探索DMLT的易感性基因,为其危害防治提供依据.方法 提取病例组（61例）及对照组（60例）淋巴细胞DNA,应用降落式多聚酶链反应（PCR）扩增,结合限制性片断长度多态性检测方法和直接测序,确定其DMA及DMB等位基因型和基因型,比较两组之间DMA和DMB等位基因型和基因型出现频率.结果 病例组HLA-DMA＊0101等位基因频率（71.3%）明显高于对照组（55.0%）,差异有统计学意义（P＜0.05）;病例组HLA-DMB＊0103等位基因频率（11.5%）明显高于对照组（3.3%）,差异有统计学意义（P＜0.05）;对照组HLA-DMA＊0102-＊0102纯合子比例明显高于病例组,差异有统计学意义（P＜0.05）;病例组HLA-DMB＊0101-＊0102杂合子比例明显低于对照组,差异有统计学意义（P＜0.05）.结论 DM基因多态性可能与DMLT的易感性有关.     

HLA-DM基因多态性调查及其与HLA-DRB_1基因的连锁分析

目的:探讨贵州地区汉族人群HLA-DM基因多态性分布,并分析其与HLA-DRB1基因间是否存在连锁不平衡关系。方法:用多聚酶链反应限制性片段长度多态性技术分析106例贵州地区汉族正常人的HLA-DM基因型;同时用序列特异性引物PCR技术检测其HLA-DRB1基因型。结果:贵州地区汉族人群中DMA*0101～0103等位基因频率分布依次为0.745、0.231和0.024,DMA基因型0101/0101和0101/0102频率分布较高者(分别为0.547和0.349);DMB*0101～0104等位基因频率分布依次为0.547、0.165、0.217和0.071,DMB基因型频率分布较高者依次为0101/0101、0101/0102和0101/0103(频率分别为0.311、0.208和0.189);DMA*0102与DRB1*08及DMA*0102与DRB1*12之间连锁不平衡参数分别为2.09和5.07。结论:贵州地区汉族人群中HLA-DM等位基因频率分布以HLA-DMA*0101～0102、HLA-DMB*0101～0103为主,DM基因型分布以DMA*0101/0101、0101/0102和DMB*0101/0101、0101/0102、0101/0103为主;贵州地区汉族人群中HLA-DM基因与HLA-DRB1基因之间存在连锁不平衡关系。     

海南汉族人群HLA-DM基因多态性与结核病的相关性

目的探讨HLA-DM基因多态性与海南汉族人群结核病的相关性。方法用多聚酶链反应-限制性片段长度多态性(Polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)技术分析90例结核病人和96例汉族健康人群的HLA-DM等位基因及基因型。结果结核病人组与健康对照组间HLA-DM等位基因频率及基因型频率无显著性差异(P0.05)。结论HLA-DM基因多态性与结核病易感性之间无显著相关关系。     

HLA-DM mediates peptide exchange by interacting transiently and repeatedly with HLA-DR1

The peptide editor HLA-DM (DM) catalyzes the exchange of peptides bound to MHC class II molecules within antigen presenting cells by generating a “peptide-receptive” MHC class II conformation (MHC_receptive) to which peptides readily bind and rapidly unbind. While recent work has uncovered the determinants of DM recognition and effector functions, the nature of MHC_receptive and its interaction with DM remains unclear. Here, we show that DM induces but does not stabilize MHC_receptive in the absence of peptides. We demonstrate that DM is out-competed by certain superantigens, and increasing solvent viscosity inhibits DM-induced peptide association. We suggest that DM mediates peptide exchange by interacting transiently and repeatedly with MHC class II molecules, continually generating MHC_receptive. The simultaneous presence of peptide and DM in the milieu is thus crucial for the efficient generation of specific peptide–MHC class II complexes over time.     

HLA-DM基因多态性及其与变应性鼻炎的相关性

目的:对变应性鼻炎患者作HLA-DM分型,探讨HLA-DM基因与变应性鼻炎遗传易感性的可能关系.方法:采用限制性片段长度多态性方法对69例无亲缘关系的变应性鼻炎病人和91例无血缘关系的健康汉族人作HLA-DM分型.结果:汉族变应性鼻炎患者及正常人DMA、DMB均以DMA*0101和DMB*0101为主,变应性鼻炎患者组DMA和DMB各等位基因和基因型与正常对照组差异无显著性(P＞0.05).结论:本组病例未能证实变应性鼻炎与HLA-DM基因有关联性.     

HLA-DMB alleles and haplotypes in Ecuador (Cuenca) Amerindians: Importance for HLA and disease studies

HLA-DMB allele frequencies and HLA-DBM-DRB1-DQB1 extended haplotypes were studied for the first time in Amerindians (Cuenca city area, Ecuador). It was found that most common extended haplotypes gathered the most frequent HLA-DRB1 Amerindian alleles. HLA-DMB polymorphism studies may be important to uncover HLA and diseases pathogenesis and also in an extended HLA haplotype frameshift. HLA-DM molecule has a crucial role together with CLIP protein in HLA class II peptide presentation. HLA extended haplotypes including complement and non classical genes alleles are proposed to HLA and disease studies.