The T cell
surface glycoprotein CD4 plays an important role in mediating cellular immunity and serves as the receptor for human immunodeficiency virus. In order to identify primary sequences within the
CD4 molecule that may be involved in the binding of the HIV-I envelope, we synthesized various
peptides corresponding to the V1, V2, V3, and V4 domains of CD4. We tested the ability of these
peptides to block the binding of purified HIV-I gp120 to CD4+ human
lymphoblastic leukemia cells (CEM) using fluorescence-activated cell sorting. One of these
peptides, corresponding to CD4
amino acids (74-95), when preincubated with gp120, blocked its subsequent binding to CEM cells by 80%. A truncated form of this
peptide (81-95), was found to be as efficient as the longer
peptide (74-95) in inhibiting the binding of gp120 to CEM cells. The same
peptide did not block the binding of
OKT4A or Leu3A anti-CD4
monoclonal antibodies, which were previously shown to block HIV-I binding to CD4. The
peptides were also tested for their ability to block HIV-I
infection of a T cell line in vitro. Only CD4
peptide (74-95) and the shorter fragment (81-95) succeeded in protecting T cells against
infection with different HIV-I strains. All the other
peptides examined had no effect on gp120 binding to CEM cells and did not block syncytia formation. Goat polyclonal
antibodies against the CD4
peptide (74-95) gave modest interference of gp120 binding to CEM cells. These data suggest that the CD4 region (74-95) participates in the CD4-mediated binding and/or internalization of HIV-I virion.