Identification of a phosphopeptide in bovine αs1-casein digest as a factor influencing proliferation and immunoglobulin production in lymphocyte cultures

Digestion of bovine alpha(s1)-casein with bovine trypsin produced peptide(s) with an inhibitory effect on concanavalin A-induced proliferation of mouse spleen cells. One of these peptides was isolated from the alpha(s1)-casein digest following ultrafiltration, hydroxyapatite chromatography and reversed-phase HPLC, and amino acid composition and sequence analyses showed it to be sequence 59-79 from the phosphoserine-rich region of alpha(s1)-casein. The isolated peptide significantly inhibited the concanavalin a-induced proliferation of mouse spleen cells and rabbit Peyer's patch cells, whereas it enhanced the lipopolysaccharide- and phytohaemagglutinin-induced proliferation of both cells. The peptide displayed mitogenic activity in the cell cultures without the commercial mitogen; and significantly enhanced immunoglobulin production. Moreover, residues 1-25 from the phosphoserine-rich region of bovine beta-casein had a similar effect on the proliferation of mouse spleen cells and rabbit Peyer's patch cells stimulated or not stimulated by the commercial mitogen. These results indicate that caseinophosphopeptides may act as a humoral immunostimulator in cell cultures.