| Abstract
| - Many non-classical, or class Ib, MHC molecules, including those linked to the cell membrane via glycosylphosphatidylinositol (GPI) membrane anchors, are poor stimulators of primary cytotoxic T cell responses. Some studies have suggested that certain amino acid substitutions in the α3 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 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-2Kb molecules in which the amino acid sequence of the α3 domain is identical to that of transmembrane H-2Kb remain less effective stimulators of a primary T cell response than membrane-spanning H-2Kb molecules. Secondly, using CD8− responder T cell hybridomas and responder T cells from transgenlc mice expressing a CD8-independent TCR, we can show that the poor stimulatory ability of GPI-linked H-2Kb 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.
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