Common epitope in human immunodeficiency virus (HIV) I-GP41 and HLA class II elicits immunosuppressive autoantibodies capable of contributing to immune dysfunction in HIV I-infected individuals.

作者：Hana Golding, G M Shearer, K Hillman, Paul A. Lucas, Jody F. Manischewitz, Robert A. Zajac, Mario Salvatore Clerici, Ronald E. Gress, R N Boswell, Basil Golding · 发表于：Journal of Clinical Investigation · 年份：1989 · DOI：10.1172/jci114034 · 被引用次数：152 · 研究领域：HIV Research and Treatment、Immune Cell Function and Interaction、Monoclonal and Polyclonal Antibodies Research

We previously reported the identification of highly conserved homologous regions located in the carboxy terminus of the HIV I gp4l-envelope (aa 837-844), and the amino-terminal of the beta chain of all human HLA class II antigens (aa 19-25).Murine monoclonal antibodies, raised against synthetic pep- tides from these homologous regions, bound not only to the isolated peptides, but also to the native gpl60 and class II molecules.In this study one-third of sera from HIV I-infected individuals, at different disease stages, were found to react with both the gp4l and class II-derived peptides.These sera also reacted with "native" HLA class II molecules.The potential affects of such autoantibodies on normal immune functions were examined.It was found that in the presence of class II- cross-reactive (but not control) sera, the proliferative re- sponses of normal CD4' T cells to tetanus toxoid and alloge- neic stimuli were markedly decreased.In addition, these sera could eliminate class II-bearing cells by antibody dependent cellular cytotoxicity.Similar affects were seen with affinitypurified IgG antibodies from patients' sera.Thus, the "molecular mimicry" between HIV I and HLA class II antigens, may lead to the generation of autoantibodies in HIV I-infected individuals that may contribute to the early functional impairment of CD4' T cell observed in many HIV I-infected individuals.