T cell activation is a main component of adaptive immunity,which involves two types of signals transmitted by key immune receptors upon engagement with their respective ligands present on the antigen-presenting cells(APCs)[1].The first signal is induced via the T cell receptor(TCR)upon binding to antigenic peptide-major histocompatibility complex(pMHC);the second signal is induced via the costimulatory receptors,the prototype of which is CD28,which can bind to either B7-1(also known as CD80)or B7-2(also known as CD86)[2,3].CD28 is the only B7 receptor constitutively expressed on naive T cells.Co-stimulation through CD28 is critically required for these cells to achieve clonal expansion,cytokine production and for protection against apopto-sis and anergy[2,3].However,despite many years of study,the relationship between the TCR and CD28-mediated pathways remains to be elucidated.It is considered that CD28 contributes both quantitatively and qualitatively to the signaling pathways driving T cell activation[2].On the other hand,several studies sug-gested that the TCR engagement facilitates CD28-B7 interactions[4,5]and consequently boosts the co-stimulatory signal initiation.It is noteworthy,however,that many of the previous studies have investigated the CD28-mediated signal transductions in previously stimulated T cell blasts or established T cell lines,but very rarely in naive T cells.Here,we investigated the mechanism of CD28-medi-ated signaling pathway activation focusing on the regulation of CD28 binding activity to B7 ligands in mouse naive CD4+T cells.