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Current Research


Early studies were aimed at elucidating the structure/function relationships of mutant MHC class I molecules in order to better understand the recognition of antigen by the T-cell receptor (TcR) molecules expressed on cytotoxic T lymphocytes (CTLs) and the subsequent triggering events leading to cell-mediated cytotoxicity with specific lysis of antigen-presenting "target" cells, such as virally-infected cells or tumor cells (1).

Later studies were aimed at elucidating the structure/function relationships of the antibody Fcg receptor (FcgR) molecules expressed on natural killer (NK) lymphocytes in order to better understand the recognition of antibodies by these molecules and the subsequent triggering events leading to antibody-dependent cell-mediated cytotoxicity (ADCC) with specific lysis of antibody-coated "target" cells, such as virally-infected cells or tumor cells (2).

The studies of Fc receptor molecules have recently been extended by the cloning and characterization of cDNA molecules encoding both murine and rat FcgR molecules as expressed on macophages (3) and NK cells (4). By joining the cDNA sequence encoding the extracellular portion of an FcgR molecule to the DNA sequence encoding the heavy-chain Fc region of an IgG antibody molecule, hybrid FcgR/IgG(Fc) proteins, called receptorbodies, have been genetically engineered for a number of potential applications including the analysis of the binding interactions between FcgR and antibody molecules. This interaction is known to involve certain segments of the antibody molecule, as illustrated below, but the corresponding interacting segments on FcgR molecules are only poorly defined at present since an exact three-dimensional model of an FcgR molecule is yet to be determined.


Figure 1 Figure 1
Figure 1

The most recent studies have turned attention to the interaction between Fas ligand (FasL) and its receptor, Fas. FasL binding to Fas triggers programmed cell death or "apoptosis" of Fas-expressing cells and this interaction appears to play a part in CTL target cell killing and is also particularly important for maintaining homeostasis of immune cell populations in general. FasL and Fas are members of a larger cytokine/cytokine receptor family that includes several immunologically significant molecules such as tumor necrosis factor (TNF; also referred to as TNF-a) and lymphotoxin-a (LT-a; also referred to as TNF-b) and their corresponding receptors TNF-R1 (p55) and TNF-R2 (p75).

Figure 2

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