| First Author | Pagán AJ | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 6 | Pages | 2909-17 |
| PubMed ID | 22896637 | Mgi Jnum | J:189943 |
| Mgi Id | MGI:5447271 | Doi | 10.4049/jimmunol.1103231 |
| Citation | Pagan AJ, et al. (2012) CD28 promotes CD4+ T cell clonal expansion during infection independently of its YMNM and PYAP motifs. J Immunol 189(6):2909-17 |
| abstractText | 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-kappaB 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. |
