Conservation of a polyanion binding site in mammalian and avian CD4.
A polyanion binding site was identified recently on human CD4 which is distinct from the human immunodeficiency virus (HIV)-gp120 binding region but which incorporates the first two immunoglobulin (Ig)-like domains of the molecule. To determine if this site is conserved in other species, several polyanions that blocked monoclonal antibody (mAb) binding to human CD4 were examined for their ability to inhibit the binding of mAb to mouse, rat, pig, sheep and chicken CD4. It was found that aurintricarboxylic acid (ATA) was a particularly effective inhibitor, blocking mAb binding to human, mouse, pig, sheep and rat CD4 by greater than 90% and to chicken CD4 by 80-90%. The polyanions dextran sulphate (DxS), polyvinyl sulphate (PVS) and polyanethole sulphonate (PAS) were also effective inhibitors of anti-CD4 mAb binding in most species, although there were clear species differences in the effects obtained. The polyanions did not inhibit mAb binding to a variety of other cell-surface antigens in the different species, with the exception of sheep CD8, suggesting that the inhibitory effects observed were essentially CD4 specific. Collectively these data indicate that a polyanion binding site is conserved in mammalian and avian CD4. Comparison of the amino acid sequences of human, mouse and rat CD4 revealed that basic residues in human CD4 which could participate in a polyanion binding site are conserved in mouse and rat CD4. It is proposed that this conserved polyanion binding site of CD4 interacts with a sulphated glycosaminoglycan chain which is associated with class II major histocompatibility complex (MHC) molecules containing recently processed antigen.
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Division of Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra.
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D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000276:immunology; D015704:CD4 Antigens / Q000737:chemistry* / Q000378:metabolism; D002645:Chickens / Q000276:immunology*; D006801:Humans; D008322:Mammals / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA / Q000276:immunology; D008969:Molecular Sequence Data; D000071228:Polyelectrolytes; D011108:Polymers / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains / Q000276:immunology; D012756:Sheep / Q000276:immunology; D013045:Species Specificity; D013552:Swine / Q000276:immunology
D015704:CD4 Antigens; D000071228:Polyelectrolytes; D011108:Polymers