The conserved carboxy terminal region of HIV-1 gp120 is recognized by seronegative HIV-exposed people.

Objective: To screen HIV-positive, long-term exposed seronegative and low-risk individuals for the presence of antibodies against regions of HIV-1 gp120 that share some degree of homology with HLA.

Methods: Sera were obtained from 63 HIV-1-infected subjects [52 Centers for Disease Control and Prevention (CDC) stage 2 and 11 stages 3/4], 32 HIV-exposed uninfected (HEU) subjects and from 24 low-risk HIV-1 seronegative individuals. They were tested by a peptide-based enzyme-linked immunosorbent assay (ELISA) for reactivity against peptides derived from the HIV-1 gp120 C-terminal region that contain regions of MHC sequence/structural similarity. Ten randomly selected sera from each group were also screened for anti-class I antibodies.

Results: Thirty per cent of the long-term HIV-1-exposed seronegative individuals had antibodies against the conserved C-terminal region (C5) of HIV-1 gp120. However, sera from HEU individuals showed no reactivity against other peptides derived from the C2 region of gp120, also an HLA homologous region. Anti-C terminal gp120 antibodies were mainly of IgM subclass, although IgG-specific antibodies were also present. In addition, 70% of HEU individuals had antibodies to HLA class I molecules compared with 15% of HIV-positive patients (restricted to only those HIV-positive patients with anti C-terminal antibodies).

Conclusion: Our results suggest that antibody responses against the C-terminal region of HIV gp120 and HLA class I may represent markers of apparent natural protection against HIV-1 infection.