Salp15, biologically functional equivalents and fragments thereof, and nucleic acid molecules encoding the same are disclosed. Recombinant host cells, recombinant nucleic acids and recombinant proteins are also disclosed. Salp15 gene products and Salp15 polypeptide fragments have biological activity in modulating CD4+ T cell activation through specific binding to CD4. Thus, therapeutic methods involving modulating T cell activation using Salp15 and biologically active polypeptide fragments thereof are also disclosed. The specific binding of Salp15 and fragment peptides thereof to CD4 can inhibit HIV infection of T cells, and thus methods of using Salp15 for inhibiting HIV infection are also disclosed. Screening methods for selecting substances having an ability to modulate activation of T cells are also disclosed.