T Cell Responses Modulated Through Interaction Between CD8αα and the Nonclassical MHC Class I Molecule, TL

The thymus leukemia antigen (TL) is a nonclassical class I molecule, expressed abundantly on intestinal epithelial cells. We show that, in contrast to other major histocompatibility complex (MHC) class I molecules that bind CD8αβ, TL preferentially binds the homotypic form of CD8α (CD8αα). Thus, TL tetramers react specifically to CD8αα-expressing cells, including most intestinal intraepithelial lymphocytes. Compared with CD8αβ, which recognizes the same MHC as the T cell receptor (TCR) and thus acts as a TCR coreceptor, high-affinity binding of CD8αα to TL modifies responses mediated by TCR recognition of antigen presented by distinct MHC molecules. These findings define a novel mechanism of lymphocyte regulation through CD8αα and MHC class I.