Regulated movement of CD4 in and out of the immunological synapse

Henry Kao, Joseph Lin, Dan R. Littman, Andrey S. Shaw, Paul M. Allen

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


The mechanism underlying the transient accumulation of CD4 at the immunological synapse (IS) and its significance for T cell activation are not understood. To investigate these issues, we mutated a serine phosphorylation site (S408) in the cytoplasmic tail of murine CD4. Preventing phosphorylation of S408 did not block CD4 recruitment to the IS; rather, it blocked the ability of CD4 to leave the IS. Surprisingly, enhanced and prolonged CD4 accumulation at the supramolecular activation cluster in the contact area had no functional consequence for T cell activation, cytokine production, or proliferation. Protein kinase C θ (PKCθ)-deficient T cells also displayed enhanced and prolonged accumulation of wild-type CD4 at the IS, indicating that θ is the critical PKC isoform involved in CD4 movement. These findings suggest a model wherein recruitment of CD4 to the IS allows its phosphorylation by PKCθ and subsequent removal from the IS. Thus, an important role for PKCθ in T cell activation involves its recruitment to the IS, where it phosphorylates specific substrates that help to maintain the dynamism of protein turnover at the IS.

Original languageEnglish
Pages (from-to)8248-8257
Number of pages10
JournalJournal of Immunology
Issue number12
StatePublished - Dec 15 2008


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