NK cell expression of the killer cell lectin-like receptor G1 (KLRG1), the mouse homolog of MAFA, is modulated by MHC class I molecules.
Using a new mAb, 2F1, we characterize a mouse natural killer (NK) cell antigen termed 'killer cell lectin-like receptor G1' (KLRG1; formerly mouse MAFA or 2F1-Ag). KLRG1 is expressed on 30-60% of murine NK cells, and a small fraction of T cells, and is composed of a homodimer of glycosylated 30-38-kDa subunits. Strikingly, cell surface expression of KLRG1 by NK cells was substantially down-regulated in mice deficient for expression of class I molecules, in contrast to the Ly49 lectin-like NK receptors, which are up-regulated in class I-deficient mice. We could not demonstrate binding of KLRG1 to class I molecules in a cell-cell adhesion assay. Transgenic expression of KLRG1 under heterologous transcription elements was unaffected by class I deficiency, indicating that class I molecules do not affect the KLRG1 protein directly, and suggesting that regulation is at the level of expression of the endogenous KLRG1 gene. Evidence is presented that class I molecules regulate KLRG1 via interactions with class I-specific inhibitory Ly49 molecules and SHP-1 signaling. Thus, although KLRG1 and Ly49 molecules are both lectin-like inhibitory receptors that are regulated by class I expression, the effects of class I on the cell surface expression of the molecules are opposing, and the underlying regulatory mechanisms are distinct.
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Department of Molecular and Cell Biology and Cancer Research Laboratory, University of California, Berkeley 94720-3200, USA.
Hanke
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Vance
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Cado
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Raulet
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D000818:Animals; D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D002678:Chimera; D015536:Down-Regulation; D015870:Gene Expression; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D011975:Receptors, Mitogen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055630:Receptors, NK Cell Lectin-Like; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011975:Receptors, Mitogen; D055630:Receptors, NK Cell Lectin-Like