Alternative titles; symbols
HGNC Approved Gene Symbol: KLRD1
Cytogenetic location: 12p13.2 Genomic coordinates (GRCh38) : 12:10,238,961-10,329,608 (from NCBI)
Natural killer (NK) cells are a distinct lineage of lymphocytes that mediate cytotoxic activity and secrete cytokines upon immune stimulation. Several genes of the C-type lectin superfamily, including members of the NKG2 family, are expressed by NK cells and may be involved in the regulation of NK cell function. See NKG2A (161555). To study CD94, an antigen preferentially expressed on NK cells, Chang et al. (1995) used an expression cloning strategy to isolate an IL2-activated polyclonal NK cell line cDNA encoding CD94. Northern blot analysis revealed that CD94 is expressed as 3 major transcripts of 0.8, 1.8, and 3.5 kb and a minor transcript of 5.5 kb in NK cell lines. The predicted protein contains a 147-amino acid extracellular domain with several motifs characteristic of C-type lectins, a 26-amino acid transmembrane domain, and a 7-amino acid cytoplasmic domain. CD94 is classified as a type II membrane protein because it has an external C terminus. The amino acid sequence of CD94 is 27 to 32% identical to those of NKG2 family members NKG2A, NKG2C (KLRC2; 602891), NKG2D (602893), and NKG2E (KLRC3; 602892). Chang et al. (1995) stated that the virtual absence of a cytoplasmic domain implies that CD94 function requires association with other receptors. Lazetic et al. (1996) demonstrated that CD94 forms disulfide-bonded heterodimers with NKG2A, NKG2C, and NKG2E.
Rodriguez et al. (1998) reported that the CD94 gene contains 6 exons. Using S1 nuclease protection and primer extension assays, they found that transcription initiation in CD94 is heterogeneous, but is restricted to a 60-bp region around the major initiation site.
Chang et al. (1995) mapped the CD94 gene to chromosome 12 using a somatic cell hybrid panel. By analysis of a cosmid contig, Plougastel and Trowsdale (1998) found that the CD94 gene is located at 12p13.2-p12.3, within the NK complex, a cluster of C-type lectin genes preferentially expressed in NK cells.
The protein HLA-E (143010) is a nonclassical MHC molecule of limited sequence variability. Its expression on the cell surface is regulated by the binding of peptides derived from the signal sequence of some other MHC class I molecules. Braud et al. (1998) reported the identification of ligands for HLA-E. Braud et al. (1998) constructed tetramers in which recombinant HLA-E and beta-2 microglobulin were refolded with an MHC leader-sequence peptide, biotinylated, and conjugated to Extravidin. This HLA-E tetramer bound to natural killer (NK) cells and a small subset of T cells from peripheral blood. On transfectants, the tetramer bound to the CD94/NKG2A, CD94/NKG2B, and CD94/NKG2C NK cell receptors, but did not bind to the immunoglobulin family of NK cell receptors (KIRs; see 604936). Surface expression of HLA-E was enough to protect target cells from lysis by CD94/NKG2A+ NK cell clones. A subset of HLA class I alleles had been shown to inhibit killing by CD94/NKG2A+ NK cell clones. Only the HLA alleles that possess a leader peptide capable of upregulating HLA-E surface expression confer resistance to NK cell-mediated lysis, implying that their action is mediated by HLA-E, the predominant ligand for the NK cell inhibitory receptor CD94/NKG2A.
Braud, V. M., Allan, D. S. J., O'Callaghan, C. A., Soderstrom, K., D'Andrea, A., Ogg, G. S., Lazetic, S., Young, N. T., Bell, J. I., Phillips, J. H., Lanier, L. L., McMichael, A. J. HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature 391: 795-799, 1998. [PubMed: 9486650] [Full Text: https://doi.org/10.1038/35869]
Chang, C., Rodriguez, A., Carretero, M., Lopez-Botet, M., Phillips, J. H., Lanier, L. L. Molecular characterization of human CD94: a type II membrane glycoprotein related to the C-type lectin superfamily. Europ. J. Immun. 25: 2433-2437, 1995. [PubMed: 7589107] [Full Text: https://doi.org/10.1002/eji.1830250904]
Lazetic, S., Chang, C., Houchins, J. P., Lanier, L. L., Phillips, J. H. Human natural killer cell receptors involved in MHC class I recognition are disulfide-linked heterodimers of CD94 and NKG2 subunits. J. Immun. 157: 4741-4745, 1996. [PubMed: 8943374]
Plougastel, B., Trowsdale, J. Sequence analysis of a 62-kb region overlapping the human KLRC cluster of genes. Genomics 49: 193-199, 1998. [PubMed: 9598306] [Full Text: https://doi.org/10.1006/geno.1997.5197]
Rodriguez, A., Carretero, M., Glienke, J., Bellon, T., Ramirez, A., Lehrach, H., Francis, F., Lopez-Botet, M. Structure of the human CD94 C-type lectin gene. Immunogenetics 47: 305-309, 1998. [PubMed: 9472066] [Full Text: https://doi.org/10.1007/s002510050362]