Differential IgG Subclass Responses to Epitopes in Transmembrane Protein of HIV-1

The human IgG subclass response to epitopes of gp41, the transmembrane protein of HIV-1, was characterized. Twenty sera that reacted with a synthetic peptide, residues 583-599 of the env product, were analyzed in subclass-specific enzyme immunoassays with this and three other peptides: the inverted sequence (599-583; HIV-env:inv), an overlapping sequence (586-606), and one derived from the 3′ end of the env gene (848-863). Also, the IgG subclass reactivities with the 583-599, 586-606 and 604-625 sequences of sera from 38 patients in various stages of HIV infection were studied. IgG1 was the most prevalent subclass. Most of the few IgG2-IgG4 reactions occurred with the peptide of the strongest antigenicity, HIV-env 604-625. The sera with detectable IgG2-IgG4 reactivity were titered to allow subclass comparisons in regions below absorbance plateaus. Two sera showed proportionately higher IgG3 relative to total IgG reactivity with HIV-env 583-599 than with HIV-env 586-606, which is indirect evidence that distinct antibody populations in these sera recognize these overlapping peptide sequences. Individual differences in the antibody response to this region may affect the immunologic control of the virus. Isotype analyses can contribute to dissection of these individualities, as shown here. High IgG reactivity with HIV-env 583-599, which was linked to absence of symptoms, resided largely in the IgG1 subclass. We found no other unambiguous association between clinical status and any IgG subclass pattern.