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Molecular Biology and
Lymphocyte Biology Sections, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
Metabolism Branch and
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Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and
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Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110
We generated transgenic mice expressing a single-chain ß2-microglobulin (ß2m)-H-2Dd. The cell-surface ß2m-H-2Dd molecule was expressed on a ß2m-deficient background and reacted with appropriate mAbs. It was of the expected m.w. and directed the normal development of CD8+ T cells in the thymus of a broad TCR repertoire. It also presented both exogenously provided and endogenous peptide Ags to effector CD8+ 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-2Dd was disrupted. Thus, the sites of TCR and NK receptor interaction with H-2Dd are distinct, an observation consistent with independent modes of TCR and NK receptor evolution and function.
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