H. Liao and Z. Zhang* Pages 126 - 133 ( 8 )
In order to combat the vast array of infectious agents it may encounter, the adaptive immune system develops a tremendously diversified antibody repertoire. B cells expressing polyreactive or autoreactive antibodies are eliminated through multiple checkpoints during early B cell development. Defects in any of these checkpoints may lead to the production of polyreactive or autoreactive antibodies, and cause autoimmune diseases. However, recent studies on a panel of established HIV-1-neutralizing antibodies and a large collection of recombinant anti-gp160 antibodies derived from HIV- 1-infected individuals showed that many of these antibodies are polyreactive or autoreactive. Whether these antibodies play important roles in combating HIV-1 infection or if they are merely by-products of chronic HIV-1 infection remains to be determined. In this review, we discuss the abnormalities in adaptive immune responses against HIV-1 infection with a focus on neutralizing antibodies against different antigenic epitopes of HIV-1 proteins. We also provide insight into the functional attributes of polyreactivity and autoreactivity as common and conserved features of HIV-1-specific antibodies. Furthermore, we summarize the autoantibodies isolated from HIV-infected individuals and their associations with clinical autoimmune diseases. Finally, we consider the opportunities and drawbacks of utilizing polyreactive antibodies from HIV-infected individuals to guide strategies aimed at developing effective antibody-based vaccine and therapeutic interventions for HIV. Understanding how polyreactive and autoreactive anti- HIV-1 antibodies are generated during the course of HIV-1 infection may provide new insights that will inform future vaccine design.
Human immunodeficiency virus type 1, B cell, polyreactive antibody, autoreactive antibody, neutralizing antibody, autoimmune diseases.
Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Department of Pediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy, Ministry of Education Key Laboratory of Birth Defects, Sichuan University, Chengdu, Sichuan, 610041