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Mouse Ly-49D recognizes H-2D(d) and activates natural killer cell cytotoxicity

  1. Author:
    Nakamura, M. C.
    Linnemeyer, P. A.
    Niemi, E. C.
    Mason, L. H.
    Ortaldo, J. R.
    Ryan, J. C.
    Seaman, W. E.

  2. Author Address

    Nakamura MC Vet Adm Med Ctr, Immunol Arthrit Sect 4150 Clement St San Francisco, CA 94121 USA Vet Adm Med Ctr, Immunol Arthrit Sect San Francisco, CA 94121 USA Univ Calif San Francisco, Dept Med San Francisco, CA 94143 USA NCI, Expt Immunol Lab, Frederick Canc Res & Dev Ctr Frederick, MD 21701 USA Univ Calif San Francisco, Dept Microbiol & Immunol San Francisco, CA 94143 USA
    1. Year: 1999
  2. Journal: Journal of Experimental Medicine
    1. 189
    2. 3
    3. Pages: 493-500
  4. Type of Article: Article
  1. Abstract:

    Although activation of natural killer (NK) cytotoxicity is generally inhibited by target major histocompatibility complex (MHC) class I expression, subtle features of NK allorecognition suggest that NK cells possess receptors that are activated by target MHC I. The mouse Ly-49D receptor has been shown to activate NK cytotoxicity, although recognition of MHC class I has not been demonstrated previously. To define Ly-49D-ligand interactions, we transfected the mouse Ly-49D receptor into the rat NI( line, RNK-16 (RNK.mLy-49D). As expected, anti-Ly-49D monoclonal antibody 12A8 specifically stimulated redirected lysis of the Fc receptor-bearing rat target YB2/0 by RNK.mLy-49D transfectants. RNK.mLy-49D effectors were tested against YB2/0 targets transfected with the mouse MHC I alleles H-2D(d), D-b, K-k, or K-b. RNK.mLy-49D cells lysed YB2/0.D-d targets more efficiently than untransfected YB2/0 or YB2/0 transfected with D-b, K-k, or K-b. This augmented lysis of H-2D(d) targets was specifically inhibited by F(ab')(2) anti-Ly-49D (12A8) and F(ab')(2) anti-H-2D(d) (34-5-8S). RNK.mLy-49D effecters were also able to specifically lyse Concanavalin A blasts isolated from H-2(b) mice (BALB/c, B10.D2, and DBA/2) but not from H-2(b) or H-2(k) mice. These experiments show that the activating receptor Ly-49D specifically interacts with the MHC I antigen, H-2D(d), demonstrating the existence of alloactivating receptors on murine NK cells. [References: 39]

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