NK and CTL Recognition of a Single Chain H-2D super(d) Molecule: Distinct Sites of H-2D super(d) Interact with NK and TCR

We generated transgenic mice expressing a single-chain beta sub(2)-microglobulin ( beta sub(2)m)-H-2D super(d). The cell-surface beta sub(2)m-H-2D super(d) molecule was expressed on a beta sub(2)m-deficient background and reacted with appropriate mAbs. It was of the expected m.w. and directed the normal development of CD8 super(+) T cells in the thymus of a broad TCR repertoire. It also presented both exogenously provided and endogenous peptide Ags to effector CD8 super(+) T cells. In tests of NK cell education and function, it failed to reveal any interaction with NK cells, suggesting that the site of the interaction of NK receptors with H-2D super(d) was disrupted. Thus, the sites of TCR and NK receptor interaction with H-2D super(d) are distinct, an observation consistent with independent modes of TCR and NK receptor evolution and function.