FUNCTIONAL EPITOPE ANALYSIS OF THE HUMAN CD4 MOLECULE - ANTIBODIES THAT INHIBIT HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GENE-EXPRESSION BIND TO THE IMMUNOGLOBULIN CDR3-LIKE REGION OF CD4

We recently demonstrated that monoclonal antibody (MAb) 13B8-2, specific for the immunoglobulin (Ig) complementary determining region 3 (CDR3)-like region of the CD4 molecule, inhibits viral transcription in human immunodeficiency virus (HIV)-infected CEM cells and HIV type 1 (HIV-1) promoter activity, Here, we have studied the capacity of several MAb specific for the D1 domain of CD4, including anti-CDR2-like (Leu-3a and ST4) and anti-CDR3-like (13B8-2 and ST40) MAb, and for the D2 domain of CD4 (BW) to inhibit both provirus transcription in HTV-1(LAI)-infected CEM cells and transcription of the chloramphenicol acetyltransferase (CAT) gene under control of the HIV-1 long terminal repeat in transiently transfected CEM cells, We found that HIV-1 promoter activity and provirus transcription are inhibited only by MAb that bind to the CDR3-like region in domain 1 of CD4, Moreover, we demonstrated that the Fab fragment of an anti-CDR3-like region-specific anti-CD4 MAb is a powerful inhibitor of HIV-1 promoter activity, These results have implications for understanding the role of the CDR3-like region in CD4 T-cell signaling, which controls provirus transcription.