Identification of a CD4 binding site on the beta 2 domain of HLA-DR molecules.
The CD4 and CD8 molecules are transmembrane glycoproteins expressed by functionally distinct subsets of mature T cells. CD4+ and CD8+ T cells recognize antigens on major histocompatibility complex (MHC) class II-bearing and class I-bearing target cells respectively. The ability of monoclonal antibodies against CD4 and CD8 to block antigen recognition by T cells, as well as cell-cell adhesion assays, indicate that CD4 and CD8 bind to nonpolymorphic determinants of class II or class I MHC. Here we demonstrate that soluble recombinant HLA-DR4 molecules from insect cells and HLA-DR-derived peptides bind to immobilized recombinant soluble CD4. CD4 binds recombinant soluble DR4 heterodimers, as well as the soluble DR4-beta chain alone. Furthermore, two out of twelve DR4-beta peptides could interact specifically with CD4. These findings show that CD4 interacts with a region of MHC class II molecules analogous to a previously identified loop in class I MHC proteins that binds CD8 (refs 8, 9).
Cammarota
G
G
International Institute of Genetics and Biophysics, Italy.
Scheirle
A
A
Takacs
B
B
Doran
D M
DM
Knorr
R
R
Bannwarth
W
W
Guardiola
J
J
Sinigaglia
F
F
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism*; D002846:Chromatography, Affinity; D015804:HLA-DR4 Antigen / Q000378:metabolism*; D015151:Immunoblotting; D066298:In Vitro Techniques; D007313:Insecta; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity
D015704:CD4 Antigens; D015804:HLA-DR4 Antigen; D011994:Recombinant Proteins