Interaction of CD4 with HLA class II antigens and HIV gp120

  title={Interaction of CD4 with HLA class II antigens and HIV gp120},
  author={Dominique Piatier‐Tonneau and Louis No{\"e}l Gastinel and François Amblard and Marianne Wojcik and Pierre Vaigot and Charles Auffray},
We have developed a cellular adhesion assay in which B lymphocytes expressing HLA class II antigens form rosettes with COS cells expressing high levels of cell surface CD4 upon transient transfection with a CDM8-CD4 plasmid construct. The assay is specific, quantitative, and overcomes the difficulties encountered with a previously described system using an SV40 viral vector. Rosette formation was inhibited by a series of CD4- and HLA-DR-specific antibodies, as well as by human immunodeficiency… Expand
Genetic variability of the human CD4 V2 domain
The genetic variability of the first two CD4 domains was addressed in a sample of the general population, and in two cohorts of HIV-seronegative and seropositive hemophiliacs by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis. Expand
Study of disabling T-cell activation and inhibiting T-cell-mediated immunopathology reveals a possible inverse agonist activity of CD4 peptidomimetics.
The structure-activity relationship of mimetics reveals that a minor change in the net hydropathic value is enough to alter the dynamic nature of the receptor-ligand complex, and it is proposed that CD4-Cys andCD4-Ser are classical antagonists, but CD 4-Met may possess properties of an inverse agonist. Expand


Interaction between CD4 and class II MHC molecules mediates cell adhesion
The CD4 protein, even in the absence of T-cell receptor-antigen interactions, can interact directly with class II antigens to function as a cell surface adhesion molecule. Expand
soluble form of CD4 (T4) protein inhibits AIDS virus infection
An efficient expression system is described in which a recombinant, soluble form of CD4 (sCD4) is secreted into tissue culture supernatants and binds to the envelope glycoprotein (gpllO) of HIV and inhibits the binding of virus to CD4+ lymphocytes, resulting in a striking inhibition of virus infectivity. Expand
Class II MHC molecules and the HIV gp 120 envelope protein interact with functionally distinct regions of the CD4 molecule.
Anti‐CD4 antibody blocking experiments clearly indicated that distinct regions of CD4 interact respectively with gp120 and with class II MHC molecules. Expand
Identification of human CD4 residues affecting class II MHC versus HIV-1 gp120 binding
The ability of gp120 to inhibit the binding of class II MHC to CD4 could be important in disrupting normal T-cell physiology, acting both to inhibit immune responses and to prevent differentiation of CD4+CD8+ thymocytes into CD4 +CD8− T lymphocytes. Expand
Functional interaction between human T-cell protein CD4 and the major histocompatibility complex HLA-DR antigen
A xenogeneic system in which human CD4 complementary DNA was transfected into the murine CD4−, CD8− T-cell hybridoma 3DT-52, strongly indicates that CD4:HLA-DR binding occurs in this system and that this interaction augments T- cell activation. Expand
The MHC-binding and gp120-binding functions of CD4 are separable.
It should be possible to design CD4 analogs that can block HIV infectivity but intrinsically lack the ability to affect the normal immune response by binding to class II MHC molecules. Expand
Highly efficient neutralization of HIV with recombinant CD4-immunoglobulin molecules
The generation of molecules which combine the specificity of CD4 and the effector functions of different immunoglobulin subclasses are described and it is found that the pentameric CD4–IgM chimaera is at least 1,000-fold more active than its dimeric CD4.–IgG counterpart in syncytiurm inhibition assays. Expand
Cell-cell adhesion mediated by CD8 and MHC class I molecules
A cell-cell binding assay is developed that measures adhesion of human B-cell lines expressing MHC class I molecules to transfected cells expressing high levels of human CDS, showing that CDS directly binds to MHCclass I molecules. Expand
A binding site for the T-cell co-receptor CD8 on the α3 domain of HLA-A2
Adhesion measurements between CD8 and 48 point mutants of HLA-A2.1 show that the CD8 α-chain binds to the α3 domain of HLA-A2.1. Three clusters of α3 residues contribute to the binding, with anExpand
Delineation of a region of the human immunodeficiency virus type 1 gp120 glycoprotein critical for interaction with the CD4 receptor
Using in vitro mutagenesis, it is found that deletion of 12 amino acids from this region of gp120 leads to a complete loss of binding and a single amino acid substitution in this region results in significantly decreased binding, suggesting that sequences within this region are directly involved in the binding of gp 120 to the CD4 receptor. Expand