Improbability of harmful autoimmune responses resulting from immunization with HIV-1 envelope glycoproteins.
Improbability of harmful autoimmune responses resulting from immunization with HIV-1 envelope glycoproteins.
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HIV-1 包膜糖蛋白免疫不可能产生有害的自身免疫反应。
DOI：
10.1089/aid.1993.9.1195
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发表时间：
1993
影响因子：
1.5
通讯作者：
Jiang,S
中科院分区：
文献类型：
--
作者：
Neurath,AR;Strick,N;Li,YY;Jiang,S
由HIV-1包膜糖蛋白gp120/gp160引起的交叉反应性抗体介导的自身免疫已被假定为有助于AIDS的发病机制。gp120/gp160与包括MHC抗原和免疫球蛋白在内的几种人类宿主蛋白之间的部分氨基酸序列同源性已被认为是免疫交叉反应性的基础。来自HIV-1感染个体的血清的抗体与选定的宿主蛋白和/或衍生自它们的合成肽的结合以及在测量T细胞的功能活性的测定中这些血清的抑制活性为自身免疫假说提供了明显的支持，这也与抗HIV-1疫苗的安全性问题有关。考虑到检测到的自身抗体可能由于对gp120/gp160的抗体应答以外的原因而产生，使用超免疫兔抗gp120/gp160和单克隆抗体研究了gp120/gp160与相关宿主蛋白之间的免疫交叉反应性。根据多克隆抗gp120的稀释终点比较确定，抗gp120与CD4的交叉反应性不可检测（<10 - 5%）。抗gp120/gp160抗体与HLA-I和HLA-II抗原的交叉反应性也未检出（<4 x 10 - 4%），与其他报告与gp120/gp41具有部分序列同源性的人蛋白的交叉反应性≤ 0.013%。在测量增殖性T细胞应答的功能测定中，抗gp120/gp160没有可检测的抑制作用。因此，用gp120/gp160免疫不太可能引起有害的自身免疫反应。
Autoimmunity mediated by cross-reactive antibodies, elicited by HIV-1 envelope glycoproteins gp120/gp160, has been postulated to contribute to the pathogenesis of AIDS. Partial amino acid sequence homology between gp120/gp160 and several human host proteins, including MHC antigens and immunoglobulins, has been perceived as the basis for immunological cross-reactivity. Binding of antibodies from sera of HIV-1-infected individuals to selected host proteins and/or to synthetic peptides derived from them and the inhibitory activity of such sera in assays measuring the functional activity of T cells provided apparent support for the autoimmunity hypothesis, which is also relevant to the issue of safety of anti-HIV-1 vaccines. Considering the possibility that the detected autoantibodies may arise for reasons other than antibody responses to gp120/gp160, the immunological cross-reactivity between gp120/gp160 and the relevant host proteins was investigated using hyperimmune rabbit anti-gp120/gp160 and monoclonal antibodies. As determined from dilution end-point comparisons for polyclonal anti-gp120, the cross-reactivity of anti-gp120 with CD4 was undetectable (<10-5%). The cross-reactivity of anti-gp120/gp160 with HLA-I and HLA-II antigens was also undetectable (<4 x 10-4%) and that with other human proteins reported to have partial sequence homology with gp120/gp41 was ≤0.013%. Anti-gp120/gp160 did not have detectable inhibitory effects in functional assays measuring proliferative T cell responses. Therefore, immunization with gp120/gp160 is unlikely to elicit harmful autoimmune responses.