Nishimura Y, Oiso M, Fujisao S, Kanai T, Kira J, Chen Y Z, Matsushita S
Department of Neuroscience and Immunology, Kumamoto University Graduate School of Medical Sciences, Japan.
Int Rev Immunol. 1998;17(5-6):229-62. doi: 10.3109/08830189809054404.
Recent advances in knowledge of crystal structures of MHC class II molecules has advanced understanding of the molecular basis for interactions between peptides and HLA class II molecules. Polymorphism of HLA class II molecules influences structures of peptides bound to HLA class II molecules. To better understand mechanisms related to particular HLA class II alleles and autoimmune diseases, it is important to identify self-peptides presented by disease-susceptible HLA class II molecules and triggering disease-causative autoreactive T cells. Autoimmune diseases occur in Caucasians, Blacks and Asians, albeit with a different incidence. In some autoimmune diseases, disease-susceptible HLA class II alleles are closely related but different, and clinical manifestations of diseases differ among ethnic groups. These phenomena strongly suggest that difference in autoimmune self-peptide(s) in the context of disease-susceptible HLA class II molecules may explain the different clinical manifestations of diseases. Therefore, a comparison among disease-susceptible HLA class II alleles, autoimmune self-peptides and clinical manifestations of autoimmune diseases in different ethnic groups would be instructive. We directed efforts to determining: (1) HLA-class II alleles specific to Asian populations and which are associated with susceptibility to autoimmune diseases, (2) binding-peptide motifs for these HLA class II molecules, and (3) self-peptides presented by susceptible HLA class II molecules to stimulate autoreactive T cells related to the development of autoimmune diseases in Asians. In this review, our related recent investigations are described and the uniqueness of HLA class II-associated autoimmune diseases in Asians is given emphasis.
近年来，对MHC II类分子晶体结构的认识取得了进展，这增进了我们对肽与HLA II类分子相互作用分子基础的理解。HLA II类分子的多态性会影响与HLA II类分子结合的肽的结构。为了更好地理解与特定HLA II类等位基因和自身免疫性疾病相关的机制，识别由疾病易感性HLA II类分子呈递并触发致病自身反应性T细胞的自身肽非常重要。自身免疫性疾病在白种人、黑人和亚洲人中均有发生，尽管发病率有所不同。在一些自身免疫性疾病中，疾病易感性HLA II类等位基因密切相关但又有所不同，且不同种族的疾病临床表现也存在差异。这些现象强烈表明，在疾病易感性HLA II类分子背景下自身免疫性自身肽的差异可能解释了疾病不同的临床表现。因此，比较不同种族中疾病易感性HLA II类等位基因、自身免疫性自身肽和自身免疫性疾病的临床表现将具有指导意义。我们致力于确定：（1）亚洲人群特有的、与自身免疫性疾病易感性相关的HLA II类等位基因；（2）这些HLA II类分子的结合肽基序；（3）易感性HLA II类分子呈递的自身肽，以刺激与亚洲人自身免疫性疾病发展相关的自身反应性T细胞。在这篇综述中，我们描述了近期的相关研究，并强调了亚洲人HLA II类相关自身免疫性疾病的独特性。
