Mouse Ly-49D recognizes H-2Dd and activates natural killer cell cytotoxicity

Area of Science:

• Immunology
• Cellular and Molecular Immunology
• NK Cell Biology

Background:

• Natural killer (NK) cell cytotoxicity is typically inhibited by target Major Histocompatibility Complex (MHC) class I expression.
• Subtle aspects of NK allorecognition suggest the existence of activating receptors for target MHC I.
• The mouse Ly-49D receptor's ability to activate NK cytotoxicity was known, but its MHC class I ligand was unidentified.

Purpose of the Study:

• To define the specific ligand interactions of the activating mouse Ly-49D receptor.
• To investigate whether Ly-49D recognizes Major Histocompatibility Complex (MHC) class I molecules.
• To demonstrate the existence of alloactivating receptors on murine NK cells.

Main Methods:

• Transfection of the mouse Ly-49D receptor into the rat NK line RNK-16 (RNK.mLy-49D).
• Testing RNK.mLy-49D transfectants against target cells expressing specific mouse MHC class I alleles (H-2Dd, Db, Kk, Kb).
• Inhibition assays using anti-Ly-49D and anti-H-2Dd antibodies to confirm specificity.

Main Results:

• RNK.mLy-49D cells demonstrated enhanced lysis of target cells expressing the H-2Dd allele compared to other MHC I alleles or untransfected cells.
• This augmented lysis was specifically inhibited by antibodies against Ly-49D and H-2Dd.
• RNK.mLy-49D effectors specifically lysed Concanavalin A blasts from H-2(d) mice but not from H-2(b) or H-2(k) mice.

Conclusions:

• The activating receptor Ly-49D specifically interacts with the MHC class I antigen H-2Dd.
• This interaction leads to the activation of NK cell cytotoxicity.
• Provides evidence for alloactivating receptors on murine NK cells involved in MHC class I recognition.