THE CYSTEINE RESIDUES IN THE CYTOPLASMIC TAIL OF CD8-ALPHA ARE REQUIRED FOR ITS CORECEPTOR FUNCTION

The cytoplasmic segment of the CD8 alpha polypeptide includes both a c ysteine-containing motif that is required for its association with the tyrosine kinase p56lck, and two serine residues which are likely to b e phosphorylated and involved in inside-out signaling phenomena. To de termine the relative importance of these residues for CD8 function, a mouse T cell hybridoma expressing a T cell receptor specific for the c lass I major histocompatibility product H-2K(b) was transfected with a set of CD8 alpha chain genes encoding polypeptides in which the cytop lasmic cysteine or serine residues were substituted with alanine. When challenged with K(b)-transfected L cells, T cell transfectants expres sing CD8 alphabeta or CD8 alphaalpha dimers with substituted cytoplasm ic serine residues responded nearly as well as wild-type CD8 transfect ants. In marked contrast, the CD8 alpha polypeptides bearing substitut ions of both cytoplasmic cysteine residues were totally impaired in th eir ability to complement the co-expressed T cell receptor.