HLA-Ⅰ等位基因对HIV-1特异性细胞毒性T细胞免疫应答的影响

摘要

Objective To investigate the impacts of human leukocyte antigen-Ⅰ(HLA-Ⅰ ) alleles on HIV-1 specific cytotoxic T lymphocyte(CTL) immune responses.Methods Frequency of interferon-γ secreting cells in PBMC stimulated with a peptide pool containing 12 overlapping peptides in HIV-1 P24 from 100 cases of HIV-1-infected individuals were detected by enzyme-linked immunospot.Meanwhile,HLA-Ⅰ A/B/Cw alleles of them were assayed by PCR-SSP method.Results Among HLA-A alleles,the HIV-1 antigen specific CTL positive responding ratss in HLA-A * rare,-A *11,-A * 33 were 57.1%,55.0%,50.8%,and there was no remarkable difference(x2 = 2.874,P ＞ 0.05 ).Among HLA-A/B/Cw alleles,the high response rates in HLA-A * rare,HLA-B * 58,HLA-Cw * 07 were 57.1%,61.9%,52.8%.Among HLA-B alleles,HLA-B * 18,-B * 40,-B * 58 alleles could induce strong HIV-1 antigen specific CTL immune responses,especially those with HLA-B * 18/-B * 40 heterozygote.Conclusions HIV-1 specific CTL immune responses seem independent to distribution frequency of HLA-A/B/Cw alleles.HLA-B allele genotypes may influence significantly on HIV-1 specific CTL immune responses.HLA-B * 58,-B * 40,-B * 18 alleles may be HLA-Ⅰ restriction sites.Moreover,HLA-B * 40/-B * 18 heterozygote may have advantage on induction of HIV-1 specific CTL immune responses.%目的 探讨中国人群HLA-Ⅰ等位基因对HIV-1抗原特异性CTL免疫应答的影响.方法 采用酶联免疫斑点(ELISPOT)技术,以HIV-1 P24区域的12个重叠肽段作为特异性肽段表位,刺激100例HIV-1感染者的外周血单核细胞(PBMC),检测IFN-γ分泌细胞频率;并用PCR特异性引物扩增法测定上述研究对象的HLA-Ⅰ A/B/Cw等位基因型,并根据基因型分布频率将HIA-Ⅰ等位基因分为常见基因型和不常见基因型.结果 在HLA-A等位基因中,HIV-1抗原特异性CTL阳性应答率由高到低为表达不常见基因HLA-A*rare(57.1%)、-A*11(55.0%)和-A*33(50.8%),各组之间比较差异无统计学意义(x2=2.874,P＞0.05).在HLA-A/B/Cw等位基因中,具有高应答率的分别为HLA-A*rare(57.1%)、HLA-B*58(61.9%)和HLA-Cw*07(52.8%).在HLA-B等位基因中,携带HLA-B*18、-B*40和-B*58基因型的感染者具有较强的HIV-1抗原特异性CTL应答,以HLA-B*18/-B*40杂合状态的感染者更为明显.结论 HIV-1感染者的特异性CTL应答似乎与HLA-A/B/Cw等位基因分布频率无关;HLA-B等位基因显著影响HIV-1感染者的特异性CTL应答;HLA-B*58、-B*40、-B*18基因型可能是HIV-1肽段表位的限制性HLA-Ⅰ位点,其中HLA-B*40/-B*18杂合状态的感染者对HIV-1表位的特异性CTL应答可能更具有优势.