Human Leukocyte Antigens (HLAs) play an important role in host immune responses to infectious pathogens, and influence organ transplantation, cancer and autoimmune diseases. In this study we conducted a high resolutio...Human Leukocyte Antigens (HLAs) play an important role in host immune responses to infectious pathogens, and influence organ transplantation, cancer and autoimmune diseases. In this study we conducted a high resolution, sequence-based genotyping of HLA class I and class II genes of more than 2000 women from Kenya, eastern Tanzania and southern Uganda around Lake Victoria and analyzed their allele, phenotype and haplotype frequencies. A considerable genetic diversity was observed at both class I and II loci. A total of 79 HLA-A, 113 HLA-B, 53 HLA-C, 25 HLA-DPA1, 60 HLA-DPB1, 15 HLA-DQA1, 44 HLA-DQB1 and 38 HLA-DRB1 alleles have been identified. The most common class I alleles were A * 02:01:01 (10.90%), B * 58:02 (8.79%), and C * 06:02:01 (16.98%). The most common class II alleles were DPA1*01:03:01 (40.60%), DPB1 * 01:01:01 (23.45%), DQA1 * 01:02:01 (31.03%), DQB1 * 03:01:01 (21.79%), DRB1 * 11:01:02 (11.65%), DRB3 * 02:02:01 (31.65%), DRB4 * 01:01:01 (10.50%), and DRB5 * 01:01:01 (10.50%). Higher than expected homozygosity was observed at HLA-B (P = 0.022), DQA1 (P = 0.004), DQB1 (P = 0.023), and DRB1 (P = 0.0006) loci. The allele frequency distribution of this population is very similar to the ones observed in other sub-Saharan populations with the exception of lower frequencies of A * 23 (5.55% versus 11.21%) and DQA1 * 03 (4.79% versus 11.72%), and higher frequencies of DPB1 * 30 (2.26% versus 0.37%) and DRB1 * 11 (21.51% versus 15.89%). The knowledge of the diversity and allele/ phenotype frequencies of the HLA alleles of this east African population, can contribute to the understanding of how host genetic factors influence disease susceptibility and effective anti-retroviral treatment of HIV infections and future vaccine trials.展开更多
动物实验证实协同刺激分子CD80(B7-1)是促进抗肿瘤免疫应答的重要分子.本文应用RT-PCR,FACS技术检测了人肿瘤细胞系及EBV转化的B细胞CD80的表达,结果表明除Raji细胞、EBV转化的B细胞CD80阳性外,3AO、MCF-7、MDA-453、MKN-45、Hela细胞...动物实验证实协同刺激分子CD80(B7-1)是促进抗肿瘤免疫应答的重要分子.本文应用RT-PCR,FACS技术检测了人肿瘤细胞系及EBV转化的B细胞CD80的表达,结果表明除Raji细胞、EBV转化的B细胞CD80阳性外,3AO、MCF-7、MDA-453、MKN-45、Hela细胞均为阴性.用我室建立的CD80逆转录病毒载体转染包装细胞PA317,筛选高滴度病毒上情感染人肿瘤细胞,得到CD80阳性表达的肿瘤细胞克隆.利用转染前后的人乳腺癌细胞系MDA-453作ICAM-I、HLA class Ⅰ、classⅡ分子表达的分析,结果表明转染有CD80基因的MDA-453细胞ICAM-Ⅰ、HLA classⅠ分子表达上调,class Ⅱ分子的表达未见改变.展开更多
文摘Human Leukocyte Antigens (HLAs) play an important role in host immune responses to infectious pathogens, and influence organ transplantation, cancer and autoimmune diseases. In this study we conducted a high resolution, sequence-based genotyping of HLA class I and class II genes of more than 2000 women from Kenya, eastern Tanzania and southern Uganda around Lake Victoria and analyzed their allele, phenotype and haplotype frequencies. A considerable genetic diversity was observed at both class I and II loci. A total of 79 HLA-A, 113 HLA-B, 53 HLA-C, 25 HLA-DPA1, 60 HLA-DPB1, 15 HLA-DQA1, 44 HLA-DQB1 and 38 HLA-DRB1 alleles have been identified. The most common class I alleles were A * 02:01:01 (10.90%), B * 58:02 (8.79%), and C * 06:02:01 (16.98%). The most common class II alleles were DPA1*01:03:01 (40.60%), DPB1 * 01:01:01 (23.45%), DQA1 * 01:02:01 (31.03%), DQB1 * 03:01:01 (21.79%), DRB1 * 11:01:02 (11.65%), DRB3 * 02:02:01 (31.65%), DRB4 * 01:01:01 (10.50%), and DRB5 * 01:01:01 (10.50%). Higher than expected homozygosity was observed at HLA-B (P = 0.022), DQA1 (P = 0.004), DQB1 (P = 0.023), and DRB1 (P = 0.0006) loci. The allele frequency distribution of this population is very similar to the ones observed in other sub-Saharan populations with the exception of lower frequencies of A * 23 (5.55% versus 11.21%) and DQA1 * 03 (4.79% versus 11.72%), and higher frequencies of DPB1 * 30 (2.26% versus 0.37%) and DRB1 * 11 (21.51% versus 15.89%). The knowledge of the diversity and allele/ phenotype frequencies of the HLA alleles of this east African population, can contribute to the understanding of how host genetic factors influence disease susceptibility and effective anti-retroviral treatment of HIV infections and future vaccine trials.
基金Projects(42077254, 51874144) supported by the National Natural Science Foundation of ChinaProjects(cstc2019jcyjmsxm X0488, cstc2021jcyj-msxm X0354) supported by the Natural Science Foundation of Chongqing,China+2 种基金Projects(KJZD-K202201304, KJQN202201314) supported by Science and Technology of Chongqing Municipal Education Commission,ChinaProject (2021M693751) supported by China Postdoctoral Science FoundationProject (P2017JG18) supported by Major Cultivation of Chongqing University of Arts and Sciences,China。
文摘动物实验证实协同刺激分子CD80(B7-1)是促进抗肿瘤免疫应答的重要分子.本文应用RT-PCR,FACS技术检测了人肿瘤细胞系及EBV转化的B细胞CD80的表达,结果表明除Raji细胞、EBV转化的B细胞CD80阳性外,3AO、MCF-7、MDA-453、MKN-45、Hela细胞均为阴性.用我室建立的CD80逆转录病毒载体转染包装细胞PA317,筛选高滴度病毒上情感染人肿瘤细胞,得到CD80阳性表达的肿瘤细胞克隆.利用转染前后的人乳腺癌细胞系MDA-453作ICAM-I、HLA class Ⅰ、classⅡ分子表达的分析,结果表明转染有CD80基因的MDA-453细胞ICAM-Ⅰ、HLA classⅠ分子表达上调,class Ⅱ分子的表达未见改变.
