Unprimed T cells are inefficiently stimulated by glycosylphosphatidylinositol-linked H-2Kb because of its lipid anchor rather than defects in CD8 binding
Many non-classical, or class Ib, MHC molecules, including those linked to the cell membrane via glycosylphosphatldylinositol (GPI) membrane anchors, are poor stimulators of primary cytotoxic T cell responses. Some studies have suggested that certain amlno acid substitutions in the <x3 domains of class Ib molecules may adversely affect their ability to interact with CD8, thereby affecting their ability to stimulate CD8 + T cells. In this report we show that poor stimulation by GPI-linked class I
... GPI-linked class I MHC molecules is not simply due to a failure to interact with CD8, but to a fundamental difference in the way T cells respond to GPI-anchored class I molecules. We have demonstrated this In two ways. Firstly, we have shown that GPI-linked H-2K b molecules In which the amlno acid sequence of the <x3 domain is identical to that of transmembrane H-2K b remain less effective stimulators of a primary T cell response than membrane-spanning H-2K b molecules. Secondly, using CDS" responder T cell hybridomas and responder T cells from transgenic mice expressing a CDB-lndependent TCR, we can show that the poor stimulatory ability of GPI-linked H-2K b molecules Is unrelated to their ability to interact with either CD8 or the TCR. These results suggest that the transmembrane linkage of class I MHC molecules plays an important role in the initial priming of T cells.