Identification of a CD4 binding site on the beta 2 domain of HLA-DR molecules

Nature. 1992 Apr 30;356(6372):799-801. doi: 10.1038/356799a0.


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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • CD4 Antigens / metabolism*
  • Chromatography, Affinity
  • HLA-DR4 Antigen / metabolism*
  • Immunoblotting
  • In Vitro Techniques
  • Insecta
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Recombinant Proteins / metabolism
  • Substrate Specificity


  • CD4 Antigens
  • HLA-DR4 Antigen
  • Recombinant Proteins