CD28 promotes CD4+ T cell clonal expansion during infection independently of its YMNM and PYAP motifs

Antonio J. Pagán, Marion Pepper, H. Hamlet Chu, Jonathan M. Green, Marc K. Jenkins

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

CD28 is required for maximal proliferation of CD4+ T cells stimulated through their TCRs. Two sites within the cytoplasmic tail of CD28, a YMNM sequence that recruits PI3K and activates NF-κB and a PYAP sequence that recruits Lck, are candidates as transducers of the signals responsible for these biological effects. We tested this proposition by tracking polyclonal peptide: MHCII-specific CD4+ T cells in vivo in mice with mutations in these sites. Mice lacking CD28 or its cytoplasmic tail had the same number of naive T cells specific for a peptide:MHCII ligand as wild-type mice. However, the mutant cells produced one tenth as many effector and memory cells as wild-type T cells after infection with bacteria expressing the antigenic peptide. Remarkably, T cells with a mutated PI3K binding site, a mutated PYAP site, or both mutations proliferated to the same extent as wild-type T cells. The only observed defect was that T cells with a mutated PYAP or Y170F site proliferated even more weakly in response to peptide without adjuvant than wild-type T cells. These results show that CD28 enhances T cell proliferation during bacterial infection by signals emanating from undiscovered sites in the cytoplasmic tail.

Original languageEnglish
Pages (from-to)2909-2917
Number of pages9
JournalJournal of Immunology
Volume189
Issue number6
DOIs
StatePublished - Sep 15 2012

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