Analysis of influence of HLA-B broad specific Bw4 motif on HCV specific T cell response

Abstract

Objective To study the influence of Bw4 broad specific motif on hepatitis C virus (HCV) specific T cell response.Methods The 86 patients with HCV infection were enrolled in this study,who had history of non-standard paid blood donation.The sequence specific primer SSP-PCR and specific primer Amplification Refractory Mutation system was used to analyze HLA type.The T cell response,using PBMCs stimulated by HCV nonstructural protein NS3,NS4 and NS5 was tested by ELISPOT assay.Results There were 29 (33.7％) cases with homozygosity Bw4/4,38 cases (44.2％) with heterozygosity Bw4/6 and 19(22.1％) cases with homozygosity Bw6/6 in 86 patients with HCV infection.HCV viral loads in Bw4/4group,Bw4/6 group and Bw6/6 group were (3.98±0.32) Log (copy/ml),(5.22± 0.29) Log (copy/ml),(5.04±0.38) Log(copy/ml),respectively and there was a significant difference in HCV load among three groups(P=0.0153).The 24 cases with HCV infection were test HCV specific T cell response divided homozygosity Bw4/4 group and non-homozygosity Bw4/4 group.The HCV specific T cell response frequency in homozygosity Bw4/4 group and non-homozygosity Bw4/4 group was 50％ (5/10) and 14.28％ (2/14,respectively.The HCV specific T cell response magnitude in homozygosity Bw4/4 group and non-homozygosity Bw4/4 group was 70 SFU/106 PBMC (0-2020 SFU/106 PBMC)and 0 SFU/106 PBMC (0-200 SFU/106 PBMC).The response magnitude and frequency in homozygosity Bw4/4 group was significantly higher than that of non-homozygosity Bw4/4 group,P value was 0.0450 and 0.069,respectively.In homozygosity Bw4/4 group NS5 induced T cell response was dominant.The NS5 specific T cell response frequency in Bw4/4 group and non-Bw4/4 group was 50％ and 7.14％,respectively,and the difference was nearly significant(P=0.050).Conclusion The HCV-infected blood donors with homozygosity for HLA-Bw4 alleles is associated with a significant lower HCV virus load and stronger HCV specific T cell response,compared with non-homozygosity Bw4/4 group. Key words: Hepatitis virus C; HLA; ELISPOT; T cell response