Genetic analysis of monoclonal antibody and HIV binding sites on the human lymphocyte antigen CD4

Saturation mutagenesis and a complement fixation selection have yielded CD4 point mutants with impaired antibody and human immunodeficiency virus binding. The patterns of amino acid substitution, in conjunction with previous antibody cross-blocking data, affirm the similar tertiary structures of the CD4 amino-terminal domain and immunoglobulin variable regions. Single residue substitutions affecting virus binding and syncytium formation are observed over an eight residue segment located in a portion of the molecule homologous to the second hypervariable region of an antibody combining site.