T cell responses modulated through interaction between CD8 alpha alpha andthe nonclassical MHC class I molecule, TL

The thymus leukemia antigen (TL) is a nonclassical class I molecule, expres sed abundantly on intestinal epithelial cells. We show that, in contrast to other major histocompatibility complex (MHC) class I molecules that bind C D8 alpha beta, TL preferentially binds the homotypic form of CD8 alpha (CD8 alpha alpha). Thus, TL tetramers react specifically to CD8 alpha alpha -ex pressing cells, including most intestinal intraepithelial lymphocytes. Comp ared with CD8 alpha beta, which recognizes the same MHC as the T cell, rece ptor (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 mechani sm of lymphocyte regulation through CD8 alpha alpha and MHC class I.