Two distinct signals are needed to activate naive T cells; the TCR’s interaction with the antigen and the second signal, known as costimulatory, rather than the other most well investigated T-cell costimulatory molecule such as CD28, CD81 is less investigated, but it is clear that CD81 and the PI3K/AKT pathway play crucial protective roles in T cell responses during human infections. This evidence concerns the gene CD28 and infection.