Subtle Mimicry of HLA by HIV-1 GP120 – A Role for Anti HLA Antibodies?

ABSTRACT

Human immunodeficiency virus (HIV-1) infection causes progressive immune deficiency by the targeted depletion of CD4+ T cells. The mechanism by which HIV-1 achieves this is not completely understood, however chronic immune activation is understood to be an essential feature of progressive HIV-1 infection. Although the mechanism by which HIV-1 induces chronic immune activation is also unknown, a number of studies have demonstrated the in vitro and in vivo protective effects of allo immunization while the presence of antibodies specific for human leukocyte antigen (HLA) class I and II molecules have been correlated with protection from HIV-1. It is currently unclear how alloimmunisation protects the host from HIV-1 or the circumstances under which anti-HLA antibodies are protective. However, a possible mechanism in which anti-HLA antibodies may protect the host, even in the absence of viral neutralization, is by binding to the HLA-homologous regions of the HIV-1 envelope protein gp120. Gp120 demonstrates the structural and functional properties of HLA and this subtle mimicry may endow gp120 with the ability to induce allo-activation of T cells in susceptible hosts, which could increase viral replication and immune dysfunction.

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