Schatzle J D, Sheu S, Stepp S E, Mathew P A, Bennett M, Kumar V
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75235-9072, USA.
Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3870-5. doi: 10.1073/pnas.96.7.3870.
The receptor 2B4 belongs to the Ig superfamily and is found on the surface of all murine natural killer (NK) cells as well as T cells displaying non-MHC-restricted cytotoxicity. Previous studies have suggested that 2B4 is an activating molecule because cross-linking of this receptor results in increased cytotoxicity and gamma-interferon secretion as well as granule exocytosis. However, it was recently shown that the gene for 2B4 encodes two different products that arise by alternative splicing. These gene products differ solely in their cytoplasmic domains. One form has a cytoplasmic tail of 150 amino acids (2B4L) and the other has a tail of 93 amino acids (2B4S). To determine the function of each receptor, cDNAs for 2B4S and 2B4L were transfected into the rat NK cell line RNK-16. Interestingly, the two forms of 2B4 had opposing functions. 2B4S was able to mediate redirected lysis of P815 tumor targets, suggesting that this form represents an activating receptor. However, 2B4L expression led to an inhibition of redirected lysis of P815 targets when the mAb 3.2.3 (specific for rat NKRP1) was used. In addition, 2B4L constitutively inhibits lysis of YAC-1 tumor targets. 2B4L is a tyrosine phosphoprotein, and removal of domains containing these residues abrogates its inhibitory function. Like other inhibitory receptors, 2B4L associates with the tyrosine phosphatase SHP-2. Thus, 2B4L is an inhibitory receptor belonging to the Ig superfamily.
受体2B4属于免疫球蛋白超家族，存在于所有小鼠自然杀伤（NK）细胞以及具有非MHC限制细胞毒性的T细胞表面。先前的研究表明2B4是一种激活分子，因为该受体的交联会导致细胞毒性增加、γ-干扰素分泌以及颗粒胞吐作用增强。然而，最近有研究表明，2B4基因通过可变剪接编码两种不同的产物。这些基因产物仅在其胞质结构域有所不同。一种形式具有150个氨基酸的胞质尾巴（2B4L），另一种具有93个氨基酸的尾巴（2B4S）。为了确定每种受体的功能，将2B4S和2B4L的cDNA转染到大鼠NK细胞系RNK-16中。有趣的是，两种形式的2B4具有相反的功能。2B4S能够介导对P815肿瘤靶标的重定向裂解，这表明这种形式代表一种激活受体。然而，当使用单克隆抗体3.2.3（对大鼠NKRP1特异）时，2B4L的表达导致对P815靶标的重定向裂解受到抑制。此外，2B4L组成性地抑制YAC-1肿瘤靶标的裂解。2B4L是一种酪氨酸磷酸化蛋白，去除含有这些残基的结构域会消除其抑制功能。与其他抑制性受体一样，2B4L与酪氨酸磷酸酶SHP-2相关联。因此，2B4L是一种属于免疫球蛋白超家族的抑制性受体。
