School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Western Australia, Australia.
AIDS. 2013 Feb 20;27(4):519-28. doi: 10.1097/QAD.0b013e32835cb720.
Natural control of HIV infection is associated with CD8 T-cell responses to Gag-encoded antigens of the HIV core and carriage of 'protective' human leukocyte antigen (HLA)-B alleles, but some HIV controllers do not possess these attributes. As slower HIV disease progression is associated with high levels of antibodies to HIV Gag proteins, we have examined antibodies to HIV proteins in controllers with and without 'protective' HLA-B alleles.
Plasma from 32 HIV controllers and 21 noncontrollers was examined for immunoglobulin G1 (IgG1) and IgG2 antibodies to HIV proteins in virus lysates by western blot assay and to recombinant (r) p55 and gp140 by ELISA. Natural killer (NK) cell-activating antibodies and FcγRIIa-binding immune complexes were also assessed.
Plasma levels of IgG1 antibodies to HIV Gag (p18, p24, rp55) and Pol-encoded (p32, p51, p66) proteins were higher in HIV controllers. In contrast, IgG1 antibodies to Env proteins were less discriminatory, with only antigp120 levels being higher in controllers. High-level IgG2 antibodies to any Gag protein were most common in HIV controllers not carrying a 'protective' HLA-B allele, particularly HLA-B*57 (P = 0.016). HIV controllers without 'protective' HLA-B alleles also had higher plasma levels of IgG1 antip32 (P = 0.04). NK cell-activating antibodies to gp140 Env protein were higher in elite controllers but did not differentiate HIV controllers with or without 'protective' HLA-B alleles. IgG1 was increased in FcγRIIa-binding immune complexes from noncontrollers.
We hypothesize that isotype-switched (IgG2+) antibodies to HIV Gag proteins and possibly IgG1 antip32 may provide alternative or additional immune control mechanisms to HLA-restricted CD8 T-cell responses in HIV controllers.
自然控制 HIV 感染与针对 HIV 核心编码抗原的 CD8 T 细胞反应以及携带“保护性”人类白细胞抗原（HLA）-B 等位基因有关，但有些 HIV 控制器不具备这些特征。由于 HIV Gag 蛋白抗体水平较高与 HIV 疾病进展较慢相关，因此我们检查了具有和不具有“保护性”HLA-B 等位基因的 HIV 控制器中针对 HIV 蛋白的抗体。
通过 Western blot 检测和 ELISA 检测病毒裂解物中的 HIV 蛋白和重组（r）p55 和 gp140，检测来自 32 名 HIV 控制器和 21 名非控制器的血浆中的 HIV 蛋白 IgG1 和 IgG2 抗体。还评估了自然杀伤（NK）细胞激活抗体和 FcγRIIa 结合免疫复合物。
HIV 控制器的 HIV Gag（p18、p24、rp55）和 Pol 编码（p32、p51、p66）蛋白的 IgG1 抗体水平较高。相比之下，Env 蛋白的 IgG1 抗体则不太具有区分性，仅控制器中的抗 gp120 水平较高。在未携带“保护性”HLA-B 等位基因的 HIV 控制器中，针对任何 Gag 蛋白的高水平 IgG2 抗体最为常见，尤其是 HLA-B*57（P=0.016）。不具有“保护性”HLA-B 等位基因的 HIV 控制器的 IgG1 抗 p32 水平也较高（P=0.04）。精英控制器中的 gp140 Env 蛋白 NK 细胞激活抗体较高，但不能区分具有或不具有“保护性”HLA-B 等位基因的 HIV 控制器。非控制器的 FcγRIIa 结合免疫复合物中的 IgG1 增加。
我们假设针对 HIV Gag 蛋白的同种型转换（IgG2+）抗体以及可能的 IgG1 抗 p32 可能为 HIV 控制器中的 HLA 受限 CD8 T 细胞反应提供替代或额外的免疫控制机制。
