CD8αα and -αβ isotypes are equally recruited to the immunological synapse through their ability to bind to MHC class I

Bimolecular fluorescence complementation was used to engineer CD8 molecules so that CD8 alpha alpha and CD8 alpha beta dimers can be independently visualized on the surface of a T cell during antigen recognition. Using this approach, we show that CD8aa is recruited to the immunological synapse almost as well as CD8ab, but because the kinase Lck associates preferentially with CD8ab in lipid rafts, CD8 alpha alpha is the weaker co-receptor. During recognition of the strong CD8 alpha alpha ligand H2-TL, CD8 alpha alpha is preferentially recruited. Thus, recruitment of the two CD8 species correlates with their relative binding to the available ligands, rather than with the co-receptor functions of the CD8 species.