A natural killer cell receptor specific for a major histocompatibility complex class I molecule.

Target cell expression of major histocompatibility complex (MHC) class I molecules correlates with resistance to lysis by natural killer (NK) cells. Prior functional studies of the murine NK cell surface molecule, Ly-49, suggested its role in downregulating NK cell cytotoxicity by specifically interacting with target cell H-2Dd molecules. In support of this hypothesis, we now demonstrate a physical interaction between H-2Dd and Ly-49 in both qualitative and quantitative cell-cell binding assays employing a stable transfected Chinese hamster ovary (CHO) cell line expressing Ly-49 and MHC class I transfected target cells. Binding occurred only when CHO cells expressed Ly-49 at high levels and targets expressed H-2Dd by transfection. Monoclonal antibody blocking experiments confirmed this interaction. These studies indicate that the specificity of natural killing is influenced by NK cell receptors that engage target cell MHC class I molecules

A natural killer cell receptor specific for a major histocompatibility complex class I molecule.

Target cell expression of major histocompatibility complex (MHC) class I molecules correlates with resistance to lysis by natural killer (NK) cells. Prior functional studies of the murine NK cell surface molecule, Ly-49, suggested its role in downregulating NK cell cytotoxicity by specifically interacting with target cell H-2Dd molecules. In support of this hypothesis, we now demonstrate a physical interaction between H-2Dd and Ly-49 in both qualitative and quantitative cell-cell binding assays employing a stable transfected Chinese hamster ovary (CHO) cell line expressing Ly-49 and MHC class I transfected target cells. Binding occurred only when CHO cells expressed Ly-49 at high levels and targets expressed H-2Dd by transfection. Monoclonal antibody blocking experiments confirmed this interaction. These studies indicate that the specificity of natural killing is influenced by NK cell receptors that engage target cell MHC class I molecules

Cis interactions of immunoreceptors with MHC and non-MHC ligands

The conventional wisdom is that cell-surface receptors interact with ligands expressed on other cells to mediate cell-to-cell communication (trans interactions). Unexpectedly, it has recently been found that two classes of receptors specific for MHC class I molecules not only interact with MHC class I molecules expressed on opposing cells, but also with those on the same cell. These cis interactions are a feature of immunoreceptors that inhibit, rather than activate, cellular functions. Here, we review situations in which cis interactions have been observed, the characteristics of receptors that bind in trans and cis, and the biological roles of cis recognition

Allelic exclusion of Ly49-family genes encoding class I MHC-specific receptors on NK cells

An important feature of natural killer (NK) cell activity is the lysis of cells that have extinguished expression of some or all class I major histocompatibility (MHC) molecules. Accordingly, the Ly49A NK-cell antigen receptor has been shown to deliver an inhibitory signal to NK cells on encounter with Dd or Dk class I MHC on target cells. Ly49A belongs to a family of eight or more highly related, tightly linked genes. Expression of Ly49A and Ly49C, another member of the Ly49 family with distinct MHC specificity, define subpopulations of NK cells that are only partly overlapping. The mechanisms regulating the expression of LY49 family members are unknown. We show here that the Ly49A and Ly49C NK-cell receptors are each subject to allelic exclusion. Because Ly49 genes are not thought to undergo DNA rearrangement, allelic exclusion of Ly49 genes could involve a mechanism distinct from that used by B and T lymphocytes and is likely to play an important role in the genesis of a putative NK-cell repertoire specific for class I molecules