Polyreactive Antibodies in Anti-HIV-1 Responses

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.