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CD28 promotes CD4+ T cell clonal expansion during infection independently of its YMNM and PYAP motifs.
Title | CD28 promotes CD4+ T cell clonal expansion during infection independently of its YMNM and PYAP motifs. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Pagán, AJ, Pepper, M, H Chu, H, Green, JM, Jenkins, MK |
Journal | J Immunol |
Volume | 189 |
Issue | 6 |
Pagination | 2909-17 |
Date Published | 2012 Sep 15 |
ISSN | 1550-6606 |
Keywords | Amino Acid Motifs, Animals, Antigens, CD28, CD4-Positive T-Lymphocytes, Cell Differentiation, Cell Line, Transformed, Clone Cells, Cytoplasm, Epitopes, T-Lymphocyte, Histocompatibility Antigens Class II, Listeriosis, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Peptide Fragments, Signal Transduction, Up-Regulation |
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. |
DOI | 10.4049/jimmunol.1103231 |
Alternate Journal | J. Immunol. |
PubMed ID | 22896637 |
PubMed Central ID | PMC3464098 |
Grant List | R01 AI039614 / AI / NIAID NIH HHS / United States R01 HL062683 / HL / NHLBI NIH HHS / United States R01-AI39614 / AI / NIAID NIH HHS / United States R01-AI66016 / AI / NIAID NIH HHS / United States R37 AI027998 / AI / NIAID NIH HHS / United States R37-AI027998 / AI / NIAID NIH HHS / United States T32-AI07313 / AI / NIAID NIH HHS / United States T32-CA9138 / CA / NCI NIH HHS / United States |