CD8-dependent CTL require co-engagement of CD8 and the TCR for phosphatidylinositol hydrolysis, but CD8-independent CTL do not and can kill in the absence of phosphatidylinositol hydrolysis.
CD8-dependent CTL require co-engagement of CD8 and the TCR for phosphatidylinositol hydrolysis, but CD8-independent CTL do not and can kill in the absence of phosphatidylinositol hydrolysis.
复制标题
CD8 依赖性 CTL 需要 CD8 和 TCR 共同参与磷脂酰肌醇水解，但 CD8 独立性 CTL 不需要，并且可以在没有磷脂酰肌醇水解的情况下杀死细胞。
DOI：
10.1093/intimm/7.6.995
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发表时间：
1995
影响因子：
4.4
通讯作者：
Potter,TA
中科院分区：
文献类型：
--
作者：
Knall,C;Smith,PA;Potter,TA
大多数MHC I类识别和CD8+CTL杀伤靶细胞的情况都需要CD8的参与。CD8在这些事件中的作用可能与CTL与APC的粘附以及通过TCR的信号转导有关。CD8介导信号转导的确切机制仍然是个谜。同样，尚不清楚是否只有与TCR结合的同一类I分子的CD8分子参与T细胞对抗原反应的信号传导。我们研究了在转染野生型或突变型（CD8非结合）I类分子的CTL和APC相互作用过程中，CD8和TCR在诱导磷脂酰肌醇-4,5-二磷酸（PIP2）水解中的共同作用要求。我们的研究结果表明，对于传统的CD8依赖性杀伤，需要CD8和TCR的共同作用来启动pip2的水解。然而，这种共同作用的要求可以通过高密度的配体来克服，例如由高浓度的外源肽提供的配体。在这种情况下，CD8与非抗原性I类分子结合可引起pip2水解。因此，在CTL和APC之间的相互作用中，通常发生在低浓度的抗原肽中，触发pip2水解需要TCR和CD8共同作用，而CD8与非抗原I类分子的结合对T细胞内的信号传导没有显著贡献。当CD8非依赖性CTL与表达突变异体抗原分子但不表达任何非抗原I类分子的APC相互作用时，没有pip2水解。
Most instances of MHC class I recognition and target cell killing by CD8+CTL require the involvement of CD8. The role of CD8 in these events may be both for adhesion of the CTL with the APC, as well as for signal transduction through the TCR. The precise mechanism by which CD8 mediates signal transduction remains enigmatic. Similarly, it is unclear whether only the CD8 molecules which bind to the same class I molecule as the TCR contribute to signaling in the T cell responding to antigen. We have investigated the requirement for co-engagement of CD8 and the TCR in the induction of the hydrolysis of phosphatidyllnositol-4,5-bisphosphate (PIP2) during the interaction of CTL and APC transfected with either wild-type or mutant (CD8 non-binding) class I molecules. Our results show that for conventional CD8-dependent killing co-engagement of both CD8 and the TCR is required to initiate PIP2hydrolysis. This requirement for co-engagement, however, can be overcome by a high density of ligand, such as that provided by high concentrations of exogenous peptide. In such situations, the binding of CD8 to non-antigenic class I molecules can elicit PIP2hydrolysis. Therefore, during interactions between CTL and APC, which generally occur at low concentrations of antigenic peptide, triggering of PIP2hydrolysis requires TCR and CD8 co-engagement, and the binding of CD8 to non-antigenic class I molecules does not contribute significantly to signaling within the T cell. Upon interaction of CD8 independent CTL with APC which express the mutant alloantigenic molecule, but do not express any non-antigenic class I molecules, there is no PIP2hydrolysis.