KLRD1 explained

CD94 (Cluster of Differentiation 94), also known as killer cell lectin-like receptor subfamily D, member 1 (KLRD1) is a human gene.^[1]

The protein encoded by CD94 gene is a lectin, cluster of differentiation and a receptor that is involved in cell signaling and is expressed on the surface of natural killer cells in the innate immune system. CD94 pairs with the NKG2 molecule as a heterodimer. The CD94/NKG2 complex, on the surface of natural killer cells interacts with Human Leukocyte Antigen (HLA)-E on target cells.

Function

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. KLRD1 (CD94) is an antigen preferentially expressed on NK cells and is classified as a type II membrane protein because it has an external C terminus. KLRD1 has two alternatively spliced variants that differ in the presence or absence of exon 2 sequence.^[1]

Interactions

KLRD1 has been shown to interact with KLRC2.^{[2] [3]}

See also

• Cluster of differentiation
• CD94/NKG2

Further reading

• Chang C, Rodríguez A, Carretero M, López-Botet M, Phillips JH, Lanier LL . Molecular characterization of human CD94: a type II membrane glycoprotein related to the C-type lectin superfamily . European Journal of Immunology . 25 . 9 . 2433–7 . Sep 1995 . 7589107 . 10.1002/eji.1830250904 . 26887028 .
• Moretta A, Vitale M, Sivori S, Bottino C, Morelli L, Augugliaro R, Barbaresi M, Pende D, Ciccone E, Lopez-Botet M, Moretta L . Human natural killer cell receptors for HLA-class I molecules. Evidence that the Kp43 (CD94) molecule functions as receptor for HLA-B alleles . The Journal of Experimental Medicine . 180 . 2 . 545–55 . Aug 1994 . 8046333 . 2191622 . 10.1084/jem.180.2.545 .
• Phillips JH, Chang C, Mattson J, Gumperz JE, Parham P, Lanier LL . CD94 and a novel associated protein (94AP) form a NK cell receptor involved in the recognition of HLA-A, HLA-B, and HLA-C allotypes . Immunity . 5 . 2 . 163–72 . Aug 1996 . 8769479 . 10.1016/S1074-7613(00)80492-6 . free .
• Lazetic S, Chang C, Houchins JP, Lanier LL, Phillips JH . Human natural killer cell receptors involved in MHC class I recognition are disulfide-linked heterodimers of CD94 and NKG2 subunits . Journal of Immunology . 157 . 11 . 4741–5 . Dec 1996 . 10.4049/jimmunol.157.11.4741 . 8943374 . free .
• Brooks AG, Posch PE, Scorzelli CJ, Borrego F, Coligan JE . NKG2A complexed with CD94 defines a novel inhibitory natural killer cell receptor . The Journal of Experimental Medicine . 185 . 4 . 795–800 . Feb 1997 . 9034158 . 2196137 . 10.1084/jem.185.4.795 .
• Mandelboim O, Pazmany L, Davis DM, Valés-Gómez M, Reyburn HT, Rybalov B, Strominger JL . Multiple receptors for HLA-G on human natural killer cells . Proceedings of the National Academy of Sciences of the United States of America . 94 . 26 . 14666–70 . Dec 1997 . 9405670 . 25087 . 10.1073/pnas.94.26.14666 . 1997PNAS...9414666M . free .
• Rodríguez A, Carretero M, Glienke J, Bellón T, Ramírez A, Lehrach H, Francis F, López-Botet M . Structure of the human CD94 C-type lectin gene . Immunogenetics . 47 . 4 . 305–9 . Mar 1998 . 9472066 . 10.1007/s002510050362 . 9012702 .
• Le Dréan E, Vély F, Olcese L, Cambiaggi A, Guia S, Krystal G, Gervois N, Moretta A, Jotereau F, Vivier E . Inhibition of antigen-induced T cell response and antibody-induced NK cell cytotoxicity by NKG2A: association of NKG2A with SHP-1 and SHP-2 protein-tyrosine phosphatases . European Journal of Immunology . 28 . 1 . 264–76 . Jan 1998 . 9485206 . 10.1002/(SICI)1521-4141(199801)28:01<264::AID-IMMU264>3.0.CO;2-O . free .
• Braud VM, Allan DS, O'Callaghan CA, Söderström K, D'Andrea A, Ogg GS, Lazetic S, Young NT, Bell JI, Phillips JH, Lanier LL, McMichael AJ . HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C . Nature . 391 . 6669 . 795–9 . Feb 1998 . 9486650 . 10.1038/35869 . 1998Natur.391..795B . 4379457 .
• Plougastel B, Trowsdale J . Sequence analysis of a 62-kb region overlapping the human KLRC cluster of genes . Genomics . 49 . 2 . 193–9 . Apr 1998 . 9598306 . 10.1006/geno.1997.5197 .
• Furukawa H, Yabe T, Watanabe K, Miyamoto R, Akaza T, Tadokoro K, Tohma S, Inoue T, Yamamoto K, Juji T . An alternatively spliced form of the human CD94 gene . Immunogenetics . 48 . 1 . 87–8 . Jun 1998 . 9601951 . 10.1007/s002510050407 . 29944586 .
• Lanier LL, Corliss B, Wu J, Phillips JH . Association of DAP12 with activating CD94/NKG2C NK cell receptors . Immunity . 8 . 6 . 693–701 . Jun 1998 . 9655483 . 10.1016/S1074-7613(00)80574-9 . free .
• Vance RE, Kraft JR, Altman JD, Jensen PE, Raulet DH . Mouse CD94/NKG2A is a natural killer cell receptor for the nonclassical major histocompatibility complex (MHC) class I molecule Qa-1(b) . The Journal of Experimental Medicine . 188 . 10 . 1841–8 . Nov 1998 . 9815261 . 2212405 . 10.1084/jem.188.10.1841 .
• Brooks AG, Borrego F, Posch PE, Patamawenu A, Scorzelli CJ, Ulbrecht M, Weiss EH, Coligan JE . Specific recognition of HLA-E, but not classical, HLA class I molecules by soluble CD94/NKG2A and NK cells . Journal of Immunology . 162 . 1 . 305–13 . Jan 1999 . 10.4049/jimmunol.162.1.305 . 9886400 . free .
• Boyington JC, Riaz AN, Patamawenu A, Coligan JE, Brooks AG, Sun PD . Structure of CD94 reveals a novel C-type lectin fold: implications for the NK cell-associated CD94/NKG2 receptors . Immunity . 10 . 1 . 75–82 . Jan 1999 . 10023772 . 10.1016/S1074-7613(00)80008-4 . free .
• Bellón T, Heredia AB, Llano M, Minguela A, Rodriguez A, López-Botet M, Aparicio P . Triggering of effector functions on a CD8+ T cell clone upon the aggregation of an activatory CD94/kp39 heterodimer . Journal of Immunology . 162 . 7 . 3996–4002 . Apr 1999 . 10.4049/jimmunol.162.7.3996 . 10201920 . free .
• Ding Y, Sumitran S, Holgersson J . Direct binding of purified HLA class I antigens by soluble NKG2/CD94 C-type lectins from natural killer cells . Scandinavian Journal of Immunology . 49 . 5 . 459–65 . May 1999 . 10320637 . 10.1046/j.1365-3083.1999.00566.x . 28500838 . free .
• Romero P, Ortega C, Palma A, Molina IJ, Peña J, Santamaría M . Expression of CD94 and NKG2 molecules on human CD4(+) T cells in response to CD3-mediated stimulation . Journal of Leukocyte Biology . 70 . 2 . 219–24 . Aug 2001 . 10.1189/jlb.70.2.219 . 11493613 . 38552860 . free .
• Shum BP, Flodin LR, Muir DG, Rajalingam R, Khakoo SI, Cleland S, Guethlein LA, Uhrberg M, Parham P . Conservation and variation in human and common chimpanzee CD94 and NKG2 genes . Journal of Immunology . 168 . 1 . 240–52 . Jan 2002 . 11751968 . 10.4049/jimmunol.168.1.240 . free .
• Terrazzano G, Zanzi D, Palomba C, Carbone E, Grimaldi S, Pisanti S, Fontana S, Zappacosta S, Ruggiero G . Differential involvement of CD40, CD80, and major histocompatibility complex class I molecules in cytotoxicity induction and interferon-gamma production by human natural killer effectors . Journal of Leukocyte Biology . 72 . 2 . 305–11 . Aug 2002 . 10.1189/jlb.72.2.305 . 12149421 . 26932214 .

Notes and References

1. Web site: Entrez Gene: KLRD1 killer cell lectin-like receptor subfamily D, member 1.
2. Lazetic S, Chang C, Houchins JP, Lanier LL, Phillips JH . Human natural killer cell receptors involved in MHC class I recognition are disulfide-linked heterodimers of CD94 and NKG2 subunits . Journal of Immunology . 157 . 11 . 4741–5 . Dec 1996 . 10.4049/jimmunol.157.11.4741 . 8943374 . free .
3. Ding Y, Sumitran S, Holgersson J . Direct binding of purified HLA class I antigens by soluble NKG2/CD94 C-type lectins from natural killer cells . Scandinavian Journal of Immunology . 49 . 5 . 459–65 . May 1999 . 10320637 . 10.1046/j.1365-3083.1999.00566.x . 28500838 . free .