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* Laboratoire d’Immunologie, Institut de Recherches Cliniques de Montréal, Montréal, Québec, Canada;
Department of Microbiology and Immunology, McGill University, Montréal, Québec, Canada;
Laboratoire de Rétrovirologie humaine, and
Laboratoire d’Immunologie, Département de Microbiologie et Immunologie, Université de Montréal, Montréal, Québec, Canada;
¶ Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021;
|| Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032; and
# Université Hassan II, Faculté des Sciences, Casablanca, Morocco.
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.
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