Structural Diversity of Monoclonal CD4 Antibodies and Their Capacity to Block the HIV GP120/CD4 Interaction

A number of monoclonal antibodies have been raised against CD4, the receptor on T cells for the HIV envelope glycoprotein gp 120. In the present paper we describe biological activities and sequence analysis of seven CD4 MAb. Five of these MAb preparations compete with HIV/gpl20 for CD4 binding. The sequences of the variable regions for these MAb were determined in order to ascertain any correlation with selective V gene usage. A relationship was found between the expressed variable region genes and the CD4 recognition pattern. The V_H genes that are used can be subdivided into two major groups expressing either a V_H gene belonging to the J558 family or to the VGam family. The usage of the V_L genes varies, indicating that the epitope specificity is predominantly determined by the rearranged V_H genes. The distinct cross-reactivity pattern of these MAb also correlates with their capacity to block binding of recombinant gpl20 to CD4 in vitro. Although five of these MAb were able to block gpl20 binding none of the CDR sequences shows a relevant homology to the gpl20 sequence. This indicates a steric hinderence mechanism for blocking gpl20 binding and not a direct interaction with the receptor binding site on CD4. The data also confirm the failure of these MAb as a potential target for receptor mimicry.