Kundu S K, Dupuis M, Sette A, Celis E, Dorner F, Eibl M, Merigan T C
Center for AIDS Research at Stanford, Stanford University Medical Center, California 94305, USA.
AIDS Res Hum Retroviruses. 1998 Dec 20;14(18):1669-78. doi: 10.1089/aid.1998.14.1669.
The effect of patient preimmunization virus sequences on CTL responses during gp160 immunization were studied. Ten HLA-A2+, HIV+ asymptomatic patients with CD4+ T cells >500/mm3 were given two courses of HIV-1 MN rgp160 vaccine over a 2-year period. Envelope epitope-specific CTL responses, using PBMCs, were measured against peptide-coated autologous B lymphoblastoid cell lines. Optimum CTL epitopes were determined by HLA-A2-binding affinity of 9- to 10-mer peptides containing the HLA-A2.1-binding motif. Ten of the high- or intermediate-binding peptides were conserved among >50% of reported clade B HIV strains. These peptide-specific CTL activities and the patient virus sequences in peptide-coding regions were monitored. Six patients showed envelope peptide-specific CTL responses, which correlated with the presence of whole envelope antigen-specific CTL responses. Five of these patients, who showed responses to epitopes in the gp41 region (aa 814-824), had preimmunization virus similar to the vaccine sequence in this region. Three patients who did not show these epitope-specific responses had initially different sequences in the HIV gene encoding that region. The epitope-specific CTL responses appear to reflect recall responses, as only patients infected with virus containing the vaccine sequence developed them and they could be recalled with a second set of vaccine injections. This appears to be reminiscent of the concept of T cell "original antigenic sin." This vaccine was also immunogenic as measured by gp160-specific lymphocyte-proliferative responses. However, increased immune responses did not impact the HIV load or CTL epitope sequences during therapy.
研究了患者免疫前病毒序列对gp160免疫期间CTL反应的影响。10名HLA - A2 +、HIV +无症状患者，CD4 + T细胞>500/mm3，在2年期间接受了两疗程的HIV - 1 MN rgp160疫苗。使用外周血单核细胞（PBMCs）针对肽包被的自体B淋巴母细胞系测量包膜表位特异性CTL反应。通过含有HLA - A2.1结合基序的9至10聚体肽的HLA - A2结合亲和力确定最佳CTL表位。10个高结合或中等结合肽在>50%的已报道B亚型HIV毒株中保守。监测这些肽特异性CTL活性以及肽编码区的患者病毒序列。6名患者表现出包膜肽特异性CTL反应，这与全包膜抗原特异性CTL反应的存在相关。其中5名对gp41区域（氨基酸814 - 824）表位有反应的患者，其免疫前病毒在该区域与疫苗序列相似。3名未表现出这些表位特异性反应的患者在编码该区域的HIV基因中最初有不同序列。表位特异性CTL反应似乎反映了回忆反应，因为只有感染了含有疫苗序列病毒的患者才产生这些反应，并且可以通过第二组疫苗注射再次引发。这似乎让人想起T细胞“原始抗原罪”的概念。通过gp160特异性淋巴细胞增殖反应测量，该疫苗也具有免疫原性。然而，免疫反应增强在治疗期间并未影响HIV载量或CTL表位序列。
