Competition of HLA-DR and a beta 2 domain peptide for HIV envelope glycoprotein gp120 binding to CD4.
HLA class II molecules and the HIV envelope glycoprotein gp120 are ligands of CD4. Reciprocal interaction sites have been well characterized for gp120 and CD4, but require further definition for HLA class II and CD4. A major CD4 binding site encompassing amino acids 134-148 in the beta 2 domain of HLA-DR has been previously identified. Recently, we have shown, by extensive characterization of mutated CD4 molecules expressed in COS cells, that HLA class II antigens interact mainly through the HIV gp120 binding site and possibly through a second minor interaction site mapping on the same face of the molecule. Based on the direct binding in vitro of iodinated affinity-purified HLA-DR1 molecules to polystyrene immobilized human IgG3-CD4, we now report on reciprocal binding inhibition of gp120, HLA-DR1 and the DR beta 2 synthetic peptide to CD4. The results strongly suggest that gp120 and the beta 2 region (amino acids 134-148) of HLA-DR1 bind mainly to the same part of CD4 domain 1 and that the CD4 binding site of HLA-DR requires the existence of a class II homodimer. In that case, alpha 2 chain residues might interact with CD4 residues different from those involved in the binding of gp120 but located close to them in the first domain.(ABSTRACT TRUNCATED AT 250 WORDS)
Autiero
M
M
International Institute of Genetics and Biophysics, Naples, Italy.
Houlgatte
R
R
Martin
M
M
Auffray
C
C
Guardiola
J
J
Piatier-Tonneau
D
D
D000595:Amino Acid Sequence; D001665:Binding Sites; D001667:Binding, Competitive / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology* / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000378:metabolism; D015798:HLA-DR1 Antigen / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D011863:Radioimmunoassay / Q000379:methods
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D015798:HLA-DR1 Antigen; D010446:Peptide Fragments