CD28 signals through tyrosine residues in its cytoplasmic tail to promote CD4+ T cell clonal expansion during infection

Abstract

Abstract CD28 is required for maximal proliferation of CD4+ T cells stimulated through their TCRs. Polyclonal peptide: MHCII-specific CD4+ T cells in mice lacking CD28 or its cytoplasmic tail produced one tenth as many effector and memory cells as wild-type T cells after bacterial infection. However, mutations in the canonical signaling sites, the membrane proximal YMNM and distal PYAP sequences, located in the cytoplasmic tail failed to suppress T cell expansion, suggesting additional sequences are sufficient for signaling. We therefore tested the contribution of the four tyrosine (4Y) residues in the cytoplasmic tail by establishing bone marrow chimeras in which CD28-deficient donor cells were first transduced with either wild-type CD28-CFP or mutated CD28-4Y-YFP and subsequently transferred to irradiated congenically mismatched CD28-sufficient mice. CD28-4Y MHCII-specific CD4+T cells produced one tenth as many effector cells as wild-type CD28-CFP cells after infection with bacterial expressing antigenic peptides. These results implicate that the tyrosine residues located in the cytoplasmic tail are required for CD28 signal transduction in effector CD4+ T cells in vivo.