Hisatsune T, Nishijima K, Kohyama M, Kato H, Kaminogawa S
Department of Applied Biological Chemistry, University of Tokyo, Japan.
J Immunol. 1995 Jan 1;154(1):88-96.
This study demonstrates and characterizes CD8+ T cells specific to the exogenous Ag, bovine alpha s1-casein. Purified CD8+ T cells from alpha s1-casein-primed lymph node cells proliferated well in response to an alpha s1-casein derivative, trypsin-digested alpha s1-casein. CD8+ T cell repertoire for the exogenous Ag was directly demonstrated in the primary culture condition. The intact alpha s1-casein primed the responding CD8+ T cells in vivo more efficiently than the tryptic alpha s1-casein; however, the in vitro proliferative response by the intact alpha s1-casein was weaker than that of the tryptic alpha s1-casein. CD8+ T cells recognized the exogenous Ag in association with MHC class I molecules as revealed by an Ab-blocking study. The major immunodominant region for the CD8+ T cells was mapped to region 136-151 of alpha s1-casein, and peptide 136-151 primed the responding CD8+ T cells but not any CD4+ T cells. Peptide 136-151 is the CD8+ T cell-specific determinant. Upon antigenic stimulation, the exogenous Ag-specific CD8+ T cells produced a significant level of IFN-gamma, which has immune suppressive activity for IgE synthesis. Our study strongly implies that CD8+ T cells that proliferate and produce IFN-gamma in response to the exogenous Ag would play a vital role in Ag-specific immunosuppression.
本研究展示并表征了针对外源性抗原牛αs1-酪蛋白的CD8+ T细胞。从经αs1-酪蛋白致敏的淋巴结细胞中纯化得到的CD8+ T细胞,对αs1-酪蛋白衍生物胰蛋白酶消化的αs1-酪蛋白有良好的增殖反应。在外源抗原的原代培养条件下直接证明了CD8+ T细胞库。完整的αs1-酪蛋白在体内比胰蛋白酶处理的αs1-酪蛋白更有效地致敏反应性CD8+ T细胞;然而,完整的αs1-酪蛋白的体外增殖反应比胰蛋白酶处理的αs1-酪蛋白弱。抗体阻断研究表明,CD8+ T细胞与MHC I类分子结合识别外源性抗原。CD8+ T细胞的主要免疫显性区域定位于αs1-酪蛋白的136-151区域,肽段136-151致敏反应性CD8+ T细胞,但不致敏任何CD4+ T细胞。肽段136-151是CD8+ T细胞特异性决定簇。在抗原刺激下,外源性抗原特异性CD8+ T细胞产生显著水平的IFN-γ,其对IgE合成具有免疫抑制活性。我们的研究强烈表明,对外源性抗原增殖并产生IFN-γ的CD8+ T细胞在抗原特异性免疫抑制中起关键作用。