Differential clustering of CD4 and CD3zeta during T cell recognition.
Whereas T helper cells recognize peptide-major histocompatibility complex (MHC) class II complexes through their T cell receptors (TCRs), CD4 binds to an antigen-independent region of the MHC. Using green fluorescent protein-tagged chimeras and three-dimensional video microscopy, we show that CD4 and TCR-associated CD3zeta cluster in the interface coincident with increases in intracellular calcium. Signaling-, costimulation-, and cytoskeleton-dependent processes then stabilize CD3zeta in a single cluster at the center of the interface, while CD4 moves to the periphery. Thus, the CD4 coreceptor may serve primarily to "boost" recognition of ligand by the TCR and may not be required once activation has been initiated.
Krummel
M F
MF
Department of Microbiology and Immunology, Stanford University School of Medicine, and the Howard Hughes Medical Institute, Stanford, CA 94305, USA.
Sjaastad
M D
MD
Wülfing
C
C
Davis
M M
MM
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D017252:CD3 Complex / Q000378:metabolism*; D015704:CD4 Antigens / Q000378:metabolism*; D020013:Calcium Signaling; D002460:Cell Line; D003599:Cytoskeleton / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation; D018715:Microscopy, Video; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D014162:Transfection
D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins