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.
Keywords: Human immunodeficiency virus type 1, B cell, polyreactive antibody, autoreactive antibody, neutralizing
antibody, autoimmune diseases.
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