Humoral Immune Responses Against gp120

In the acute infection phase, the antibodies produced are HIV-1-type-specific, and in the years following initial infection, generally broader, but lower titered virus-neutralizing antibody responses develop which include HIV-1 strains with a divergent gp120 third hypervariable domain (V3). The V3 loop within the carboy-terminal half of gp120 contains a major neutralization domain, the principal neutralizing determinant (PND), so named according to the results obtained from the first in vitro neutralization studies. The early neutralization assays were conducted utilizing HIV-1 isolates passaged multiple times through T cell lines. Such HIV-1 strains are referenced as lab strains or T cell (T lymphocyte)-adapted strains, i.e., T cell-line-adapted (TCLA) .

Antigenic epitopes on the viral envelope surface (SU) glycoprotein (gp120) were identified using HIV-1-seropositive sera and a large panel of human monoclonal antibodies generated in vitro.

A region corresponding to the CD4-binding domain (CD4bd) and epitopes within the first and fifth conserved regions of gp120 (C1/C5) are recognized by HIV-1 isolate cross-reactive antibodies prevalent in the serum of HIV-1-seropositive individuals. Additional studies indicated that monoclonal antibody IgG1b12, specific for CD4bd, reacts with structures present on oligomeric envelope.17

It is important to note that anti-V3-loop monoclonal antibodies significantly neutralized lab strains of HIV-1 passaged in T cells.18-20 The V3 loop in primary strains does not appear accessible on the native surface envelope gp120, and therefore antibodies directed against the V3 region may not significantly neutralize HIV-1 field isolates.

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