Peptides and their constituent amino acids influence the immune response and phagocytosis in different ways

Abstract

To elucidate the role of immunoactive amino acids (which are capable of stimulating the immune response) in the peptide regulation of antibody production and phagocytic processes we have studied the influence of some fragments of natural peptides and the amino acids included in them on the thymus-dependent immune response to sheep red blood cells (SRBC) and on the phagocytosis of Staphylococcus by murine peritoneal neutrophils. It has been found that the effects of amino acids, as well as of peptides that they form, on the immune response and on phagocytosis were diverse. Glutamic and aspartic acids, threonine and valine stimulated both the immune response and phagocytosis. Glycine and isoleucine influenced neither the immune response nor phagocytosis, whereas lysine, proline, tyrosine and leucine did not influence the immune response, but enhanced the phagocytic activity of neutrophils. Arginine inhibited the immune response but stimulated phagocytosis. Peptide TTKD (the fragment 77–80 of murine Thy-1-antigen) contained in C- and N-terminus amino acids (T and D) which stimulated the antibody production and phagocytosis, and lysine (K) which stimulated phagocytosis only, enhanced both processes. Peptides LGIP and PYIK (the fragments 49–53 and 66–69 of murine Thy-1 antigen) which contained both immunologically inert amino acids (L, G, I, P, Y, K) and phagocytosis stimulating amino acids (L, Y, P, K) influenced neither the immune response nor the phagocytic activity of neutrophils. The elongation of peptide LGIP at the C-terminus with the immunologically active glutamic acid (E) resulted in the emergence of peptide LGIPE which stimulated both the immune response and phagocytosis, whereas the addition of valine which stimulated both processes, to the C-terminus of peptide PYIK resulted in the ability of peptide PYIKV to enhance phagocytosis without any influence on the immune response. At the same time peptide TKPR (tuftsin) containing threonine (which stimulated both the immune response and phagocytosis) at the N-terminus and arginine (which inhibited the immune response but stimulated phagocytosis) at the C-terminus, stimulated both antibody production and phagocytosis. These data showed that certain amino acids displayed the immunomodulating and phagocytosis stimulatory properties and that these properties determined the activity of peptides with a definite amino acids sequence. The influence of peptides and amino acids incorporated in them on the immune response differed from their influence on phagocytosis. This might be the basis for the design of the preparations with the directed action. The role of amino acids as a self-sufficient part of immunoregulation is discussed.