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Science 289 (5483): 1349-1352

Copyright © 2000 by the American Association for the Advancement of Science

Differential Clustering of CD4 and CD3zeta During T Cell Recognition

Matthew F. Krummel,1 Michael D. Sjaastad,2 Christoph Wülfing,1* Mark M. Davis1dagger

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.

1 Department of Microbiology and Immunology, Stanford University School of Medicine, and the Howard Hughes Medical Institute, Stanford, CA 94305, USA.
2 Universal Imaging Corporation, 502 Brandywine Parkway, West Chester, PA 19380, USA.
*   Present address: Center for Immunology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9093, USA.

dagger    To whom correspondence should be addressed: E-mail: mdavis{at}

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