Pedersen A E, Jacoby B F, Skov S, Claesson M H
Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Denmark.
Cell Immunol. 1996 Nov 1;173(2):295-302. doi: 10.1006/cimm.1996.0281.
We have studied the antibody-induced effect of cross-linking the major histocompatibility complex class I (MHC-I) in human T leukemic cells (Jurkat) and human B lymphoma cells (Solubo, Burkitts lymphoma) on intracellular [Ca2+]i levels. The increase in [Ca2+]i after MHC-I cross-linking in Jurkat cells and Solubo cells was dependent on both intra- and extracellular Ca2+ stores. The initial increase was dependent on intracellular stores but the long-term elevated [Ca2+]i level was due to an influx of Ca2+. The kinetics of Ca2+ release and influx was different in the two cell lines. In both cell lines the increase in [Ca2+]i after MHC-I cross-linking caused upregulation of CD69, an early marker of activation. When studying the effect of MHC-I cross-linking on the TCR- and B cell antigen receptor (BCR)- mediated increase in [Ca2+]i, respectively, we observed that MHC-I had a costimulatory effect on the TCR-mediated increase in [Ca2+]i in Jurkat cells but not on the anti-IgM-mediated activity of Solubo cells. Studies of subpopulations of Jurkat and Solubo cells expressing different levels of MHC-I on their cell surfaces revealed that the TCR- and BCR-mediated increases in [Ca2+]i, respectively, were positively correlated with the level of MHC-I expressed on the cell surface. These observations suggest two different roles in signal transduction for the MHC-I molecules in the T and B cells studied. First, by themselves MHC-I complexes are able to induce activation of intracellular second messenger systems following cross-linking. Second, threshold levels for activation through antigen receptors in T and B cells are dependent on or determined by the actual numbers of MHC-I complexes present in the cell membrane. Thus the present data strongly point to a new, physiological role for MHC-I molecules in T and B cells.
我们研究了抗体诱导的人类T白血病细胞（Jurkat）和人类B淋巴瘤细胞（Solubo，伯基特淋巴瘤）中主要组织相容性复合体I类（MHC-I）交联对细胞内[Ca2+]i水平的影响。Jurkat细胞和Solubo细胞中MHC-I交联后[Ca2+]i的增加依赖于细胞内和细胞外的Ca2+储存。最初的增加依赖于细胞内储存，但[Ca2+]i的长期升高是由于Ca2+的内流。两种细胞系中Ca2+释放和内流的动力学不同。在两种细胞系中，MHC-I交联后[Ca2+]i的增加都导致了CD69的上调，CD69是激活的早期标志物。分别研究MHC-I交联对T细胞受体（TCR）和B细胞抗原受体（BCR）介导的[Ca2+]i增加的影响时，我们观察到MHC-I对Jurkat细胞中TCR介导的[Ca2+]i增加有共刺激作用，但对Solubo细胞中抗IgM介导的活性没有作用。对Jurkat和Solubo细胞亚群的研究表明，它们在细胞表面表达不同水平的MHC-I，结果显示TCR和BCR介导的[Ca2+]i增加分别与细胞表面表达的MHC-I水平呈正相关。这些观察结果表明，在所研究的T细胞和B细胞中，MHC-I分子在信号转导中发挥两种不同的作用。首先，MHC-I复合物自身在交联后能够诱导细胞内第二信使系统的激活。其次，T细胞和B细胞中通过抗原受体激活的阈值水平依赖于或由细胞膜中存在的MHC-I复合物的实际数量决定。因此，目前的数据有力地表明了MHC-I分子在T细胞和B细胞中的一种新的生理作用。
