Functional dichotomy of a 20-mer and 16-mer peptide derived from Staphylococcus aureus protein A: importance of amino...

Protein A (PA) of Staphylococcus aureus possesses a wide variety of biological properties such as antitumor, antitoxic, anticarcinogenic, immunomodulatory, antifungal and antiparasitic. Since PA is a foreign protein, it is quite logical to assume that it may be cleaved into smaller peptide fragments in vivo, which may be responsible for the diverse biological activities of whole PA. We have shown that two proteolytic peptide fragments (20-mer and 16-mer) of PA mimics IgG binding and some of the immunomodulatory properties of PA. In the present study, we investigated upon the functional similarity and dissimilarity in these two peptides. The 16-mer peptide induces the production of IL6, IL10, TNFalpha and IL1alpha but it does not have any effect on secretion of IFNgamma and IL4. Whereas 20-mer peptide induces production of TNFalpha, IL1alpha along with induction of IFNgamma but it downregulates IL4, IL6 and IL10 production. IFNgamma to IL4 ratio clearly indicates that the 20-mer peptide induces Th1 type response, whereas 16-mer peptide induces Th0 type response. The 20-mer peptide retains the antitumor property of the native protein (PA) in Ehrlich ascitis tumor model, whereas 16-mer peptide does retain the same property only in vitro. The 16-mer peptide however can activate macrophages to kill Ehrlich ascitis tumor cells in vitro more efficiently than that of 20-mer peptide. Thus both the peptides although derived from same native protein and has had 13 aminoacid residues in common, appears to evoke different reactivites in the immune system. Thus it appears that the IgG binding ability which is seen with the native protein A molecule and also with both 16-mer and 20-mer peptides do not automatically confer upon them the antitumor property, and cytokine producing activities. Thus it appears that all different properties associated with Protein A may not be necessarily associated with its IgG binding abilities.