CD28 promotes CD4+ T cell clonal expansion during infection independently of its YMNM and PYAP motifs.
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.
Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Antonio J
AJ
Pagán
Marion
M
Pepper
H Hamlet
HH
Chu
Jonathan M
JM
Green
Marc K
MK
Jenkins
D020816:Amino Acid Motifs / Q000235:genetics / Q000276:immunology; D000818:Animals; D018106:CD28 Antigens / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002461:Cell Line, Transformed; D002999:Clone Cells; D003593:Cytoplasm / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008088:Listeriosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D018106:CD28 Antigens; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments