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Two sites within the cytoplasmic tail of CD28, a YMNM sequence that recruits PI3K and activates NF-\u03baB 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1103231","type":"journal-article","created":{"date-parts":[[2012,8,15]],"date-time":"2012-08-15T22:05:57Z","timestamp":1345068357000},"page":"2909-2917","source":"Crossref","is-referenced-by-count":33,"title":["CD28 Promotes CD4+ T Cell Clonal Expansion during Infection Independently of Its YMNM and PYAP Motifs"],"prefix":"10.1093","volume":"189","author":[{"given":"Antonio J","family":"Pag\u00e1n","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Minnesota Medical School , Minneapolis, MN 55455"},{"name":"Center for Immunology, University of Minnesota Medical School , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Pepper","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Minnesota Medical School , Minneapolis, MN 55455"},{"name":"Center for Immunology, University of Minnesota Medical School , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H Hamlet","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Minnesota Medical School , Minneapolis, MN 55455"},{"name":"Center for Immunology, University of Minnesota Medical School , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Washington University , St. Louis, MO 63110"},{"name":"Department of Pathology and Immunology, Washington University , St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc K","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Minnesota Medical School , Minneapolis, MN 55455"},{"name":"Center for Immunology, University of Minnesota Medical School , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,9,15]]},"reference":[{"key":"2025032409252981500_r1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1146\/annurev.immunol.19.1.23","article-title":"In vivo activation of antigen-specific CD4 T cells","volume":"19","author":"Jenkins","year":"2001","journal-title":"Annu. 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