Vyakarnam A, Matear P M, Cranenburg C, Michie C, Beverley P C, Wahren B, Gill S K, Weller I
Academic Department of Genito-Urinary Medicine, University College London, UK.
Int Immunol. 1991 Oct;3(10):939-47. doi: 10.1093/intimm/3.10.939.
We demonstrate that peptides (16 amino acids long) covering the sequence of the HIV-1 core protein p24 induce significant proliferation in peripheral blood mononuclear cells (PBMC) of several (greater than 50%) healthy seronegative volunteers as well as seronegative homosexual men. The nature of this response was characterized and compared with those of HIV-infected patients. Several peptides induced responses; however, the most frequent responses in both seropositive and seronegative individuals were noted to the following peptides: 1 and 2 (aa 133-157); 6 and 7 (aa 183-207); 15 (aa 273-287); and 17 and 18 (aa 293-317). The response pattern was related to the disease stage of the patients; seronegative individuals as well as asymptomatic seropositive individuals (CDC II/III) responded to low concentrations of several peptides, but symptomatic patients (CDC IV) only responded to high concentrations of a few peptides. Cell separation studies of PBMC from healthy volunteers showed that the responding cells were CD4+ and expressed the CD45RO differentiation antigen. Furthermore, cord-blood mononuclear cells with less than 5% of CD45RO T cells did not proliferative to any of the peptides. Finally, CD4+ T cell lines specific for both peptides and p24 protein were successfully established from the PBMC of seronegative individuals confirming the data obtained with freshly isolated cells. These studies therefore suggest that the CD4+ cell response to p24 is not strictly disease related, instead, the response may be due to priming of the host with cross-reactive antigens.
我们证明,覆盖HIV-1核心蛋白p24序列的肽(16个氨基酸长)可诱导数名(超过50%)健康血清阴性志愿者以及血清阴性同性恋男性的外周血单核细胞(PBMC)显著增殖。对这种反应的性质进行了表征,并与HIV感染患者的反应进行了比较。几种肽可诱导反应;然而,在血清阳性和血清阴性个体中,最常见的反应是针对以下几种肽:1和2(氨基酸133 - 157);6和7(氨基酸183 - 207);15(氨基酸273 - 287);以及17和18(氨基酸293 - 317)。反应模式与患者的疾病阶段相关;血清阴性个体以及无症状血清阳性个体(疾病控制与预防中心II/III期)对几种肽的低浓度有反应,但有症状的患者(疾病控制与预防中心IV期)仅对少数几种肽的高浓度有反应。对健康志愿者PBMC的细胞分离研究表明,有反应的细胞是CD4 + 细胞,并表达CD45RO分化抗原。此外,CD45RO T细胞少于5%的脐血单核细胞对任何一种肽都不发生增殖反应。最后,从血清阴性个体的PBMC中成功建立了对肽和p24蛋白均具有特异性的CD4 + T细胞系,证实了从新鲜分离细胞获得的数据。因此,这些研究表明,CD4 + 细胞对p24的反应并非严格与疾病相关,相反,这种反应可能是由于宿主被交叉反应性抗原致敏所致。