CD4 dimers constitute the functional component required for T cell activation.
The CD4 molecule plays a key role in the development and activation of helper T cells. Dimerization and oligomerization is often a necessary step in the function of several cell surface receptors. Herein, we provide direct biochemical evidence confirming the presence of CD4 as dimers in transfected cells from hemopoetic and fibroblastic origin as well as in primary T cells. Such dimers are also observed with murine CD4 confirming selective pressure during evolution to maintain such a structure. Using a series of point mutations, we have precisely mapped the dimerization site at residues K318 and Q344 within the fourth extracellular domain of CD4. These residues are highly conserved and their mutation results in interference with dimer formation. More importantly, we demonstrate that dimer formation is essential for the coligand and coreceptor functions of CD4 in T cell activation. These data strongly suggest that CD4 dimerization is necessary for helper T cell function.
Moldovan
Maria-Cristina
MC
Laboratoire d'Immunologie, Institut de Recherches Cliniques de Montréal, Québec, Canada.
Yachou
Abdelkader
A
Lévesque
Karine
K
Wu
Hao
H
Hendrickson
Wayne A
WA
Cohen
Eric A
EA
Sékaly
Rafick-Pierre
RP
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D015704:CD4 Antigens / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019556:COS Cells; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D019281:Dimerization; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D012641:Selection, Genetic; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014162:Transfection
D015704:CD4 Antigens; D018076:DNA, Complementary; D011948:Receptors, Antigen, T-Cell