Antigen presenting cell function in HIV-1 infected patients

Antigen presenting cell (APC) function is central to the activation of anti-viral cytotoxic T-cells and antibody production. In previous studies we have evaluated APC function in HIV-1 infected patients as the capacity to present peptide to a well defined panel of CD4 T-cell clones. We found that APC from HIV-1 infected patients were defective in the capacity to present peptide to CD4 T-cell clones. The APC defect uncovered by this method was present early in infection and worsened with increasing viral load, suggesting that it was an important determinant of progression and anti-viral efficacy. The CD4 T-cell clones were, however, found to vary in their susceptibility to the APC defect. CD4 T-cell clones that failed to respond to peptide presented by HIV + APC were 1000-fold more readily inhibited by anti-CD4 antibody than T-cell clones which consistently responded to APC from patients infected with HIV-1 (HIV + APC). An intermediate group of T-cell clones were also identified that only responded to peptide and HIV + APC from asymptomatic patients. These results suggested that the underlying mechanism for the APC defect was binding of T-cell CD4 by APC-associated gp120. In this paper we discuss the evidence to support this hypothesis.