|Ribbon / surface model of CD4 (below, yellow) with MHC II molecule according to PDB 1JL4|
Existing structure data: 1cdh , 1cdi , 1cdj , 1cdu , 1cdy , 1g9m , 1g9n , 1GC1 , 1jl4 , 1q68 , 1rzj , 1rzk , 1wio , 1wip , 1wiq , 2b4c , 2nxy , 2nxz , 2ny0 , 2ny1 , 2ny2 , 2ny3 , 2ny4 , 2ny5 , 2ny6 , 3cd4
|Properties of human protein|
|Mass / length primary structure||433 amino acids|
|Secondary to quaternary structure||single pass type 1 membrane protein|
|Gene names||CD4 ; CD4mut|
|Parent taxon||Higher mammals|
The CD4 receptor or just CD4 ( c luster of d ifferentiation 4 ) is a glycoprotein , which on the surface of cells of the immune system ( T-helper cells , monocytes and macrophages occurs). Tests that determine the number of cells that carry this molecule provide insight into the state of the immune system. When infected with the HI virus , the number of CD4-bearing immune cells decreases after a certain time. During the infection process, the CD4 molecule is one of the docking points for the HI virus.
Structure and biosynthesis
The receptor consists of four immunoglobulin domains arranged one behind the other , which protrude from the surface of the T cell, as well as a small cytoplasmic section.
CD4 is expressed not only in T cells but also in B cells , macrophages and granulocytes . Its role in normal central nervous system microglial cells is unclear.
The CD4 gene extends over 31,320 base pairs and consists of 10 exons . The mRNA is 3,006 bases in length and an enzyme with 433 amino acids is produced from it through translation and post-translational modification .
CD4 is what is known as a co-receptor of the T cell receptor . When the T cell receptor binds to an antigen presented on an MHC- II molecule by antigen presenting cells , CD4 with the extracellular domain can bind to the non-variable part of the MHC-II. It has been shown that the tyrosine kinase Lck, which phosphorylates the CD3 proteins of the T cell receptor complex after antigen binding and thus activates it, binds to the cytosolic part of the CD4 and is thus brought to the T cell receptor when the antigen is bound. CD4 thus has an important role in antigen recognition by the TCR.
With the subsequent concentration of CD3, TCR and CD4 molecules on the presented antigen and formation of the immunological synapse , CD4 remains at the periphery of the immunological synapse. The cytoplasmic part of CD4 can interact with the acidic cluster protein ( ACP33 ), which downregulates CD4 activities. CD4 induces the accumulation of lipid rafts in the membrane and possibly regulates the activation of T cells.
Function during infection with HIV
CD4 binds to the proteins gp120 and P4HB / PDI of HIV-1 and is part of the P4HB / PDI-CD4- CXCR4- gp120 complex once HIV-1 is coupled to the cell membrane. CD4 interacts with the HIV proteins gp160 and Vpu . CD4 production is shut down by the HIV proteins Nef and gp160.
However, the presence of CD4 is not sufficient for HIV-1 to infect the T cell: a human chemokine receptor, either CCR5 or CXCR4, must also be present. Microglial cells that express CD4 are damaged during infection with HIV. The mechanism is unclear.
CD4 is used in flow cytometry as a marker for T helper cells.
- ↑ a b c CD4 receptor. In: Online Mendelian Inheritance in Man . (English).
- ↑ ENSEMBL entry
- ↑ a b UniProt entry