Havran W L, Lancki D W, Moldwin R L, Dialynas D P, Fitch F W
Department of Pathology, University of Chicago, IL 60637.
J Immunol. 1988 Feb 15;140(4):1034-42.
HK1.4 mAb was identified based on its ability to stimulate proliferation of cloned murine CTL. Within the lymphoid lineage, mAb HK1.4 bound exclusively to CTL, regardless of the expression of Lyt-2 or MHC restriction. HK1.4 mAb also bound to 40% of bone marrow cells and less than 5% of thymocytes from all mouse strains tested. Based on the tissue distribution of the determinant with which it reacted and the ability to cross-block binding of the anti-Ly-6 mAb H9/25, mAb HK1.4 appeared to react with a product of the Ly-6 locus. However, significant differences were observed between the properties of mAb HK1.4 and other, previously described anti-Ly-6 mAb. Cell proliferation and lymphokine release by cloned CTL were stimulated by culture with mAb HK1.4 alone or in the presence of non-stimulatory levels of IL-2. This proliferation and lymphokine release were not blocked by the addition of soluble anti-Lyt-2 or anti-IL-2R mAb. Activation induced by HK1.4 mAb proceeds in the absence of accessory cells, of cross-linking of the TCR, or the addition of mitogens or PMA. Stimulation of cells by anti-TCR mAb was not blocked by the addition of soluble HK1.4 mAb, and the stimulatory effects of HK1.4 and anti-TCR mAb were not additive. However, IL-2-driven proliferation of CTL clones was dramatically inhibited by the addition of HK1.4 mAb.HK1.4 mAb had no effect on Ag-specific or lectin-facilitated cytolysis. Taken together, these data indicate that mAb HK1.4 operates via an IL-2-independent pathway of activation that is also independent of the TCR.
HK1.4单克隆抗体是根据其刺激克隆化小鼠细胞毒性T淋巴细胞（CTL）增殖的能力而鉴定出来的。在淋巴谱系中，HK1.4单克隆抗体仅与CTL结合，而与Lyt-2的表达或MHC限制无关。HK1.4单克隆抗体也与所有测试小鼠品系中40%的骨髓细胞以及不到5%的胸腺细胞结合。基于其反应的决定簇的组织分布以及交叉阻断抗Ly-6单克隆抗体H9/25结合的能力，HK1.4单克隆抗体似乎与Ly-6基因座的产物发生反应。然而，在HK1.4单克隆抗体和其他先前描述的抗Ly-6单克隆抗体的特性之间观察到了显著差异。单独用HK1.4单克隆抗体培养或在非刺激水平的白细胞介素-2（IL-2）存在下培养，可刺激克隆化CTL的细胞增殖和淋巴因子释放。添加可溶性抗Lyt-2或抗IL-2受体单克隆抗体并不能阻断这种增殖和淋巴因子释放。HK1.4单克隆抗体诱导的激活在没有辅助细胞、T细胞受体（TCR）交联、添加丝裂原或佛波酯（PMA）的情况下进行。添加可溶性HK1.4单克隆抗体并不能阻断抗TCR单克隆抗体对细胞的刺激，并且HK1.4和抗TCR单克隆抗体的刺激作用也不是相加的。然而，添加HK1.4单克隆抗体可显著抑制IL-2驱动的CTL克隆增殖。HK1.4单克隆抗体对抗原特异性或凝集素促进的细胞溶解没有影响。综上所述，这些数据表明HK1.4单克隆抗体通过一条不依赖IL-2且也不依赖TCR的激活途径发挥作用。
