人类白细胞抗原-HLA分型技术002.ppt

HLA分型技术 上海交通大学医学院 彭奕冰 主任技师 Significance of the MHC role in immune response role in organ transplantation role in predisposition to disease Progress in organ transplantation Genetic barriers to transplantation Principles of transplantation Minor histocompatibility antigensand graft survival Graft versus host (GVH) disease GVH disease in humans The human MHC genes The mouse MHC genes Polymorphism of MHC antigens (based on phenotype) The inheritance of MHC genes Crossing overresults in new haplotypes MHC products expressed on cells Differential expression of MHC antigens Mechanisms of graft rejection Tempo of rejection reaction A, B DR matching and graft survival HLA and disease association 细胞学分型法 细胞学分型法已被血清学和分子生物学方法代替。单相混合淋巴细胞培养实验还在使用。 分子生物学技术为基础的HLA分型法 原理 HLA的多态性是由基因中核苷酸序列突变引起的。同一基因的不同等位基因之间核苷酸序列大多是相同的，变异集中在几个DNA片段中。在这些片断中，不同的等位基因具有特定的序列。测定这些片段的DNA序列就可以确定等位基因。 变异片段 变异片段 变异片段 a b c d ac ATCGGTCAAGGCCTATCGATTGCGTAGGC bd ATCGGTCAAGGCCTATCGATTGCGTAGGC ac ATCGGTCAAGGCCTATCGATTGCGTAGGC ad ATCGGTCAAGGCCTATCGATTGCGTAGGC bc ATCGGTCAAGGCCTATCGATTGCGTAGGC 根据片段组合指定等位基因 ac ac bc ad bd ac ef gh ef ml jk ox rt wq sv zp Histocompatibility (transplantation) antigens: Antigens on tissues and cells that determine their rejection when grafted between two genetically different individuals; Major histocompatibility (MHC) antigens: Histocompatibility antigens that cause a very strong immune response and are most important in rejection; MHC complex: Group of genes on a single chromosome encoding the MHC antigens; HLA (human leukocyte antigens): MHC antigens of man (first detected on leukocytes); H?2 antigens: MHC antigens of mouse; Xenograft: Grafts between members of different species (also known as heterologous, xenogeneic or hetero- grafts); Allograft: Grafts between two members of the same species (also known as allogeneic or homo- graft); Isograft: Grafts between membe