Elucidation of immnoregulating function of casein phosphopeptide

从牛αs1-酪蛋白的胰蛋白酶消化中纯化了一种免疫调节肽，鉴定为牛αs1-酪蛋白残基59 ~ 79。序列59-79有一个富含磷酸丝氨酸的区域，被称为酪蛋白磷酸肽之一。牛β-酪蛋白也具有富磷丝蛋白区。因此，作者从胰蛋白酶β-酪蛋白中分离出酪蛋白磷酸化肽之一β-酪蛋白片段1-25，证实该肽与牛α 51 -酪蛋白中的酪蛋白磷酸化肽一样具有免疫调节作用。酪蛋白磷脂肽显示有丝分裂活性，并通过刺激小鼠脾细胞培养中Th2细胞产生的IL-5和IL-6，刺激有丝分裂原诱导的增殖和免疫球蛋白的产生。口服酪蛋白磷酸肽可提高小鼠和仔猪抗原特异性IgA和总IgA水平。此外，免疫刺激活性被证实为具有至少2个磷酸丝氨酸残基的磷酸肽，即SerP-Leu-SerP。牛酪蛋白在多种蛋白水解酶的作用下可合成多种酪蛋白磷酸肽。因此，从牛酪蛋白消化液中制备的酪蛋白磷酸肽是增强人和牲畜粘膜IgA反应的有益食品。

An immunomodulating peptide was purified from a trypsin digest of bovine αs1-casein and identified as residues 59-79 in bovine αs1-casein. The sequence 59-79 has a Phosphoserine-rich region and is called one of casein phosphopeptides. Bovine β-casein aloso possesses phosphoserin-rich region. Hence, the author isolated β-casein fragment 1-25, one of the casein phosphopeptides, from tryptic β-casein and confirmed that the phosphopeptide displayed the immunomodulating action as well as the casein phosphopeptide from bovine αs1-casein.The casein phosphopeptides displayed a mitogenic activity and stimulated the mitogen-induced proliferations and the immunoglobulin production via the stimulation of IL-5 and IL-6 produced from Th2 cells in mouse spleen cell cultures. The oral adminstration of casein phosphopeptides enhanced the levels of antigen-specific IgA and total IgA in mice and piglets. Moreover, the immunostimulating activity was confirmed to a phosphopeptide having at least 2 phosphoserine residues, i.e., SerP-Leu-SerP.It has been widely reported that various kinds of casein phosphopeptides are produced from bovine caseins by the action of various kinds of proteolytic enzymes. Thus, the casein phosphopeptides prepared from bovine casein digests are beneficial foodstuffs for the enhancement of mucosal IgA responses in man and livestock.