Natural analogue peptides of an HIV-1 GP120 T-helper epitope antagonize response of GP120-specific human CD4 T-cell clones

Neutralizing antibodies and specific cytotoxic T lymphocytes (CTL) may cont ribute to controlling viral spread, and ideally, to virus clearance in HIV infection. Both effector mechanisms depend on specific CD4 T-helper (Th) ce lls. Nevertheless, HIV hypervariability facilitates appearance of escape mu tants for antibodies and for CTL responses. Here we also show that natural mutations (i.e., from sequences of different HIV strains) in an immunodomin ant Th epitope recognized by human CD4 clones specific for the envelope gly coprotein gp120 escape CD4 T-cell recognition. Furthermore, several natural analogue peptides exert an antagonistic function by inhibiting proliferati ve response of T cells specific to gp120 with a wild-type sequence. If simi lar events occur in vivo, they may represent an additional escape mechanism for HIV. In fact, antagonism for CD4 Th response may occur during superinf ection with a different strain, or with the appearance of a variant carryin g a mutated antagonistic sequence. In both cases, impaired Th cell function could lead to reduced immune control of HIV infection by interfering with CTL and antibody response.