According to the two-signal model of T cell activation, costimulatory molecules augment T cell receptor (TCR) signaling, whereas adhesion molecules enhance TCR–MHC-peptide recognition. The structure and binding properties of CD28 imply that it may perform both functions, blurring the distinction between adhesion and costimulatory molecules. Our results show that CD28 on naïve T cells does not support adhesion and has little or no capacity for directly enhancing TCR–MHC-peptide interactions. Instead of being dependent on costimulatory signaling, we propose that a key function of the immunological synapse is to generate a cellular microenvironment that favors the interactions of potent secondary signaling molecules, such as CD28.
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We thank H. Reiser and M. Naquet for cells producing the 1610A1 and H155 antibodies, respectively; G. Freeman for the mCD80 cDNA;A. Holdorf for Jurkat cells expressing truncation mutants of murine CD28; R. Burack for sharing his unpublished results on cooperation of CD2 and CD28; R. Houdei for cell and antibody production; and R. Barrett for preparation of the manuscript. Supported by funds from the NIH, HHMI, the Whitaker Foundation and Irene Diamond.
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Bromley, S., Iaboni, A., Davis, S. et al. The immunological synapse and CD28-CD80 interactions. Nat Immunol 2, 1159–1166 (2001) doi:10.1038/ni737
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