Alternative titles; symbols
HGNC Approved Gene Symbol: KLRF1
Cytogenetic location: 12p13.31 Genomic coordinates (GRCh38): 12:9,800,052-9,845,005 (from NCBI)
KLRF1, an activating homodimeric C-type lectin-like receptor (CTLR), is expressed on nearly all natural killer (NK) cells and stimulates their cytoxicity and cytokine release (Kuttruff et al., 2009).
By screening an EST database with the KLRB1 (602890) cDNA sequence, followed by 5-prime RACE using peripheral blood leukocyte RNA, Roda-Navarro et al. (2000) obtained a cDNA encoding KLRF1. KLRF1 encodes a predicted 231-amino acid type II transmembrane protein that has a 42-amino acid cytoplasmic region containing 2 immunoreceptor tyrosine-based inhibitory motifs (ITIMs); a 23-amino acid transmembrane segment; and a 166-amino acid extracellular region containing a C-type lectin domain with the 6 invariant cys residues observed in all CTLRs. RT-PCR analysis of leukocyte mRNA suggested the presence of a KLRF1 alternative splice variant; alternative splicing occurs with other KLR genes (e.g., KLRC1; 161555). Northern blot analysis detected 1.35-, 2.5-, 7.5-, and 9.5-kb KLRF1 transcripts. The predominant 1.35-kb transcript was strongly expressed in peripheral blood leukocytes and spleen, with weaker expression in lymph node and adult liver, and no expression detected in bone marrow, thymus, and fetal liver. The KLRF1 gene was not expressed in brain, heart, placenta, lung, kidney, skeletal muscle, and pancreas. Within peripheral blood leukocyte and immunocyte cell lines, expression was predominant in NK cells but was also detected in monocytes.
By generating monoclonal antibodies and using flow cytometric and RT-PCR analyses, Welte et al. (2006) showed that NKp80 was expressed predominantly on NK cells, but also on gamma-delta T cells, and that it induced NK-cell degranulation and cytokine release. FACS and surface plasmon resonance analyses showed that AICL (CLEC2B; 603242), a myeloid cell-specific receptor, interacted with NKp80 at an intermediate on rate and a rapid off rate. AICL expression was upregulated by a number of Toll-like receptor (TLR; see 603030) ligands, but not by TLR9 (605474) ligands. Welte et al. (2006) concluded that AICL is a ligand for the activating NK receptor NKp80 and that NKp80-AICL interaction induces cytolysis of myeloid cells and activation of both NK cells and monocytes. They noted that both molecules are present in humans but not in rodents.
Using gene expression profiling and FACS analysis, Kuttruff et al. (2009) showed that NKp80 was expressed on a small but highly responsive subset of effector memory CD8 (see 186910)-positive T cells with an inflammatory NK-like phenotype and that NKp80 promoted T-cell responses toward AICL-expressing cells.
By PCR analysis of BAC clones, Roda-Navarro et al. (2000) mapped the KLRF1 gene to the NK complex on chromosome 12p13.2-p12.3, between the AICL gene (CLECSF2; 603242) and the OLR1 gene (602601).
Kuttruff, S., Koch, S., Kelp, A., Pawelec, G., Rammensee, H.-G., Steinle, A. NKp80 defines and stimulates a reactive subset of CD8 T cells. Blood 113: 358-369, 2009. [PubMed: 18922855] [Full Text: https://doi.org/10.1182/blood-2008-03-145615]
Roda-Navarro, P., Arce, I., Renedo, M., Montgomery, K., Kucherlapati, R., Fernandez-Ruiz, E. Human KLRF1, a novel member of the killer cell lectin-like receptor gene family: molecular characterization, genomic structure, physical mapping to the NK gene complex and expression analysis. Europ. J. Immun. 30: 568-576, 2000. [PubMed: 10671213] [Full Text: https://doi.org/10.1002/1521-4141(200002)30:2<568::AID-IMMU568>3.0.CO;2-Y]
Welte, S., Kuttruff, S., Waldhauer, I., Steinle, A. Mutual activation of natural killer cells and monocytes mediated by NKp80-AICL interaction. Nature Immun. 7: 1334-1342, 2006. [PubMed: 17057721] [Full Text: https://doi.org/10.1038/ni1402]