北大医学研究生课程-分子免疫学-MHC.ppt

DNA分型技术 Sequencing 序列测定 RFLP（restriction fragment length polymorphism, 限制性片段长度多态性） PCR/SSO（sequence specific oligonucleotide, 序列特异的寡核苷酸）: PCR+oligo probe hybridization PCR/SSP（sequence specific primer, 序列特异引物）：特异、简便 PCR-SSCP（single-strand conformation polymorphrism, 单链构象多态性） Tetramer技术： 十. MHC的临床应用 器官移植排斥的预防和治疗 MHC分子加抗原多肽用于抗原特异的T细胞的表位分析,T细胞的直接分离与克隆,T 细胞功能检测以及作为激活T细胞的刺激物和进行原位染色等方面的研究 MHC基因转染肿瘤细胞作为肿瘤疫苗治疗肿瘤 亲子鉴定及法医学 思考题 MHC I类抗原和II类抗原的呈递过程。 MHC的功能 MHC与疾病的发生 MHC的遗传特点 * Congenic mouse strains. Produced by repeated backcrossing of two mouse strains, in each generation selecting for a specific phenotypic trait (such as allograft rejection). * Intra-H2-recombinant congenic mouse strains. McDevitt and collaborators showed that the strength of the immune response to particular antigens was controlled by H2. By selecting in mouse crosses between H2 congenic mice for serologically detected, allelically variant H2 proteins, it was possible to show that H2 was a gene complex with a minimum 4 subregions. The efficiency of the immune response to particular antigenic proteins often mapped to the I region. * Overall organization of the Human and Chicken MHC. Human = ~200 genes in ~4Mb. Different numbers of genes in different species and sometimes individuals of a species Some class I and class II genes are highly polymorphic A dynamic gene complex * Selected MHC Class I and Class II genes are highly polymorphic, others are not. * Allelic variation in Class I (and Class II) MHC proteins is primarily in amino acid residues that surround the peptide binding cleft. A model of peptide transport begins with TAP in an inward/cytosol-facing conformation with the NBDs (nucleotide-binding domains) open. A peptide binds a cytosol-facing cavity formed by the TMDs (transmembrane domains), causing a conformational change that is transmitted to the NBDs. This conformational change permits ATP-dependent NBD closure, perhaps by facilitating exchange of ADP on TAP2 for ATP. As