Disclosed are methods and compositions for the inhibition of modulation of T cell costimulatory pathway by a pathogenic agent, particularly, the inhibition of activation of a T cell costimulatory pathway by a pyrogenic exotoxin. The direct interaction of a superantigen with a specific site within the dimer interface of a CD28 family member is inhibited using immunomodulatory peptides. Specific antagonist immunomodulatory peptides comprise amino acid sequences derived from a dimer interface of a T cell co-stimulatory pathway member, or peptides which comprise an amino acid sequence which specifically binds to an amino acid sequence within the dimer interface of a T cell co-stimulatory pathway member. Compositions comprising said peptides and methods for the treatment of immune-related disorders are also disclosed. Such molecules may be used in screening for a test substance which specifically binds to the CD28 molecule and is capable of antagonizing pyrogenic exotoxin-mediated activation of Th1 lymphocytes.