Mühlbacher M, Spruth M, Siegel F, Zangerle R, Dierich M P
Institut für Hygiene, Universität Innsbruck, Austria.
Immunobiology. 1999 Jun;200(2):295-305. doi: 10.1016/s0171-2985(99)80078-3.
This study was designed to distinguish between antibodies in HIV-1-infected patients directed against epitopes accessible on the native HIV-1 envelope (Env) complex and non-native Env epitopes. Peptide p#13 (Env. aa642-673) containing the neutralising 2F5 epitope and recombinant soluble glycoprotein 160 (rsgp160) were used in ELISA to determine the antibody (Ab) reactivity in sera of 116 HIV-1-infected individuals and 18 HIV negative controls. The reactivity of sera classified CDC stage C against p#13 was significantly decreased in comparison to stage A sera, while staying constant against rsgp160. Accordingly, in 6 out of 8 individual patients tested over time the response against p#13 was declining at later time points of infection. The reactivity of patients' sera against p#13 corresponded directly to the recognition of infected T cells and largely also to the CD4 cell count. The causal relationships of these phenomena are not clear. It is conceivable that antibodies against epitopes on HIV are lost or escape mutants arise and consequently control of HIV is lost and virus load increases as it is known for CDC stage C. Alternatively, increasing virus load may affect B cells recognising native Env epitopes and turn antibody production down by some mechanism. In this latter scenario helper T cells might have a critical role.
本研究旨在区分HIV-1感染患者体内针对天然HIV-1包膜(Env)复合物上可及表位的抗体与非天然Env表位的抗体。使用含有中和性2F5表位的肽p#13(Env. aa642 - 673)和重组可溶性糖蛋白160(rsgp160),通过酶联免疫吸附测定(ELISA)来检测116例HIV-1感染个体和18例HIV阴性对照者血清中的抗体(Ab)反应性。与A期血清相比,C类疾病控制中心(CDC)分期的血清对p#13的反应性显著降低,而对rsgp160的反应性保持不变。因此,在8例随时间进行检测的个体患者中,有6例在感染后期对p#13的反应性下降。患者血清对p#13的反应性与对感染T细胞的识别直接相关,在很大程度上也与CD4细胞计数相关。这些现象之间的因果关系尚不清楚。可以想象,针对HIV表位的抗体可能会丢失,或者出现逃逸突变体,结果如C类疾病控制中心分期所知,对HIV的控制丧失,病毒载量增加。或者,病毒载量的增加可能会影响识别天然Env表位的B细胞,并通过某种机制降低抗体产生。在后一种情况下,辅助性T细胞可能起关键作用。