Nehete P N, Johnson P C, Schapiro S J, Arlinghaus R B, Sastry K J
Department of Veterinary Sciences, University of Texas M.D. Anderson Cancer Center, Bastrop 78602, USA.
J Clin Immunol. 1996 Mar;16(2):115-24. doi: 10.1007/BF01540958.
We have investigated the proliferative response of peripheral blood mononuclear cells from individuals infected with human immunodeficiency virus type 1 (HIV-1) to synthetic peptides from the third variable loop region (V3) in the envelope protein gp120. We tested a total of 14 peptides, corresponding to 14 HIV-1 isolates belonging to four geographical locations (clades U, A, B, and D). Although differences in relative level of responses exist between individual peptides and patients, the proliferation in response to all 14 V3 peptides was significantly greater than that to unrelated control peptides. Additionally, we observed that proliferative responses of blood cells from the 10 HIV-seropositive individuals studied from the clade B region to peptides from within clades U, A, B, and D were not significantly different, indicating the cross-reactive nature of the V3-specific cell-mediated immune responses. Even though the majority of patients also exhibited antibody responses against several V3 peptides, serum samples from 50% of clade B patients exhibited antibody cross-reactivity, while proliferative responses to V3 peptides from more than one clade were observed in 80% of patients. Importantly, in two patients, decreased CD4+ cell numbers, an important surrogate marker of disease progression, significantly correlated with loss of V3 peptide-specific proliferative responses but not antibody responses. These results have important implications toward evaluating the utility of V3 peptides for designing therapeutic and/or vaccine reagents against HIV-1.
我们研究了感染1型人类免疫缺陷病毒（HIV-1）个体的外周血单核细胞对包膜蛋白gp120中第三个可变环区（V3）合成肽的增殖反应。我们总共测试了14种肽，它们对应于来自四个地理位置（U、A、B和D亚型）的14株HIV-1分离株。尽管各个肽与患者之间的相对反应水平存在差异，但对所有14种V3肽的增殖反应均显著大于对无关对照肽的反应。此外，我们观察到，对来自B亚型区域的10名HIV血清阳性个体的血细胞对U、A、B和D亚型内肽的增殖反应没有显著差异，这表明V3特异性细胞介导免疫反应具有交叉反应性。尽管大多数患者也表现出针对几种V3肽的抗体反应，但50%的B亚型患者血清样本表现出抗体交叉反应，而80%的患者观察到对来自多个亚型的V3肽的增殖反应。重要的是，在两名患者中，作为疾病进展重要替代指标的CD4 + 细胞数量减少与V3肽特异性增殖反应的丧失显著相关，但与抗体反应无关。这些结果对于评估V3肽在设计抗HIV-1治疗和/或疫苗试剂中的效用具有重要意义。
