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Humoral Immune Response
Figure 1. Above is a Jmol image of the consensus V3 loop of gp120. The partially-hidden nature of the conserved region of gp120 makes it difficult for our bodies to develope effective neutralizing antibodies. The image is from the RCSB Protein Data Bank. PDB 1CE4.
Antibodies specific to gp120 and the gp41 envelope proteins (Janeway et al, 2005) can be found in plasma of infected patients within weeks of initial infection (Paul, 2003), and may play a role in minimizing viral impact during the asymptomatic period, but are unable to clear an infection. Despite the early presence of HIV-specific antibodies, the high levels of antibodies with the ability to neutralize viruses are generally only found in long-term nonprogressors (Paul, 2003).
Two trimers of gp120 and gp41 create the envelope protein gp160, which is heavily glycosylated. CD4 T cells bind gp120 on a depression in the protein (Paul, 2003). The virus also binds chemokine receptors on another depressed site on gp120 as co-receptors. Both of these sites are highly conserved and are not glycosylated, so are thought to be the antigenic portions of the envelope protein (Paul, 2003). Moreover, these sites may remain hidden until exposure is caused by a conformational change induced by CD4 binding. Thus antibodies would remain impotent until CD4 binding exposes antigenic sites (Paul, 2003). Interestingly, a slow-progression of HIV has been associated with high levels of anti-p24 antibodies (p24 is an HIV-core antigen), but an absence of antibodies specific for certain gp120 regions (Rubbert et al, 2006). Some individuals considered "exposed, not-infected" seem to form mucosal IgA responses against HIV proteins (Rubbert et al, 2006) that may provide some neutralizing protection against transmission across mucosal surfaces.
The rapid mutation rate of HIV inhibits an effective humoral response. Antibodies capable of neutralizing the virus have been found in infected individuals, but it appears that by the time the body has produced these antibodies, mutations have occurred with different epitopes (Rubbert et al, 2006). Thus our B cells can't keep up with the virus that sidesteps every attack our body launches.
References:
Janeway, Charles A, et al. Immunobiology. 6th ed. New York: Garland Science Publishing, 2005.
Paul, William ed. Fundamental Immunology. 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2003.
Rubbert, A., et al . 2006. Pathogenesis of HIV-1 Infection. In: Hoffmann, C., Rockstroh, J., Kamps, B., editors. HIV Medicine 2006. Flying Publisher. <http://www.hivmedicine.com/index.htm>. (5 May 2007).