A CD8 polypeptide that is lost after passing the Golgi but before reaching the cell surface: a novel sorting mechanism.

The murine CD8 T cell differentiation antigen is a glycoprotein expressed on the cell surface as a heterodimer comprising the products of two closely linked genes, Ly-2 and Ly-3. The Ly-2 gene encodes, through a mechanism of alternate splicing, two polypeptide chains, alpha and alpha', that differ from one another in the lengths of their cytoplasmic tails. All T cells transcribe and translate both the alpha and alpha' polypeptides of Ly-2 and form heterodimers of each of these polypeptides disulphide-bonded with the Ly-3 polypeptide. However, there is very specific, developmentally controlled regulation of the expression of these heterodimers on the cell surface. Namely, immature T cells show no discrimination of CD8 molecules and express on their cell surface heterodimers containing the Ly-3 polypeptide linked to either the alpha or alpha' chain of Ly-2. In contrast, mature T cells express on their cell surface predominantly the heterodimer containing the Ly-2 alpha chain, the species which has a cytoplasmic tail. Moreover, in mature T cells the complexes which contain the alpha' chain are retained within the cell late in processing. These data emphasize the importance of the CD8 accessory molecule in the development of the functional T cell repertoire and uncover a novel protein sorting mechanism in mature T cells.