Viral selection pressure and CD4+T cell epitope in HLA-DRB1 * 11:01 of HCV infected patients / 中国输血杂志

ABSTRACT

【Objective】 HLA-DRB1 * 1101, as a class HLA-Ⅱ gene, was reported to be associated with spontaneous clearance of HCV in Han and Li population. Our study was to investigate the effects of viral selection pressure and CD4+T cell epitope on the natural outcome of HCV infection in HLA-DRB1 * 1101 positive infected patients. 【Methods】 The positive selection sites and population growth of E1E2 and NS3 genes of common HCV 6a in HLA-DRB1 * 1101 positive and negative groups in Guangdong were respectively analyzed. The peptide library covering the conserved regions of common HCV genotypes was used to stimulate HCV spontaneous clearance group and chronic infection group using ELISPOT method. Reactive peptides were obtained according to the number of spot-forming cells per well and the frequency of occurrence in different groups. 【Results】 The positive selection sites (PSSs) of E1E2 and NS3 of common HCV 6a in HLA-DRB1 * 1101 negative group were greater than those in HLA-DRB1 * 1101 positive group. Furthermore, the number of PPSs in CD4+T cell peptide in HLA-DRB1 * 1101 negative group were also greater than those in HLA-DRB1 * 1101 positive group; Both groups of HCV 6a had a population growth in Guangdong, and the expansion trend of HLA-DRB1 * 1101 negative group was significantly higher than that of HLA-DRB1 * 1101 positive group. Compared to HCV chronic infection group, the response rate of HCV spontaneous clearance group to five peptides (C-52 E2691-707, C-119 NS31545-1560, C-134 NS4A1669-1684, C-154 NS4B1912-1927, C-159 NS4B1929-1944) was higher. However, the HCV chronic infection group showed a higher response rate to two of the peptides(C-111 NS31497-1512, C-130 NS31650-1665). When HLA-DRB1 * 1101 typing was considered, there was no significant difference in HCV-specific immune response generated by PBMCs between HLA-DRB1 * 1101 positive and HLA-DRB1 * 1101 negative groups. 【Conclusion】 This study revealed the relationship between viral selection pressure of HLA-DRB1 * 1101 HCV infected persons and CD4+T cell antigen epitopes. At the same time, CD4+ T cell antigen epitopes of HCV pan-genotype were obtained, providing basic data for the development of T cell vaccine suitable for HCV pan-genotype.