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 CD8 alpha beta, TL preferentially binds the homotypic form of CD8 alpha (CD8 alpha alpha). Thus, TL tetramers react specifically to CD8 alpha alpha -expressing cells, including most intestinal intraepithelial lymphocytes. Compared with CD8 alpha beta, which recognizes the same MHC as the T cell, receptor (TCR) and thus acts as a TCR coreceptor, high-affinity binding of CD8 alpha alpha 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 CD8 alpha alpha and MHC class I.