The CD94 receptor, expressed on natural killer (NK) and CD8+ T cells, is known as a relatively non-polymorphic receptor with orthologues in humans, other primates, cattle, and rodents. In the house mouse (Mus musculus), a single allele is highly conserved among laboratory strains, and reports of allelic variation in lab- or wild-living mice are lacking, except for deficiency in one lab strain (DBA/2J). The non-classical MHC-I molecule Qa-1b is the ligand for mouse CD94/NKG2A, presenting alternative non-americ fragment of leader peptides (Qa-1 determinant modifier (Qdm)) from classical MHC-I molecules. Here, we report a novel allele identified in free-living house mice captured in Norway, living among individuals carrying the canonical Cd94 allele. The novel Cd94LocA allele encodes 12 amino acid substitutions in the extracellular lectin-like domain. Flow cytometric analysis of primary NK cells and transfected cells indicates that the substitutions prevent binding of CD94 mAb and Qa-1b/Qdm tetramers. Our data further indicate correlation of Cd94 polymorphism with the two major subspecies of house mice in Europe. Together, these findings suggest that the Cd94LocA/NKG2A heterodimeric receptor is widely expressed among M. musculus subspecies musculus, with ligand-binding properties different from mice of subspecies domesticus, such as the C57BL/6 strain.

• Klíčová slova
• Comparative immunology/evolution, Genomics, Inhibitory/activating receptors, MHC, NK cell,
• MeSH
• alely MeSH
• buňky NK metabolismus   MeSH
• CD8-pozitivní T-lymfocyty metabolismus   MeSH
• CHO buňky MeSH
• Cricetulus MeSH
• druhová specificita MeSH
• HEK293 buňky MeSH
• histokompatibilita - antigeny třídy I chemie   genetika   metabolismus   MeSH
• křečci praví MeSH
• lektinové receptory NK-buněk - podrodina C chemie   genetika   metabolismus   MeSH
• lektinové receptory NK-buněk - podrodina D chemie   genetika   metabolismus   MeSH
• lidé MeSH
• multimerizace proteinu MeSH
• myši inbrední C57BL MeSH
• myši inbrední DBA MeSH
• peptidy chemie   genetika   metabolismus   MeSH
• polymorfismus genetický * MeSH
• sekvence aminokyselin MeSH
• sekvenční homologie aminokyselin MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• křečci praví MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Norsko MeSH
• Názvy látek
• histokompatibilita - antigeny třídy I MeSH
• lektinové receptory NK-buněk - podrodina C MeSH
• lektinové receptory NK-buněk - podrodina D MeSH
• peptidy MeSH
• Q surface antigens MeSH Prohlížeč
• Qdm protein, mouse MeSH Prohlížeč

Human natural killer (NK) cells express on their surface several members of the C-type lectin family such as NKR-P1, CD94, and NKG2 that are probably involved in recognition of target cells and delivery of signals modulating NK cell cytotoxicity. To elucidate the mechanisms involved in signaling via these receptors, we solubilized in vitro cultured human NK cells by a mild detergent, Brij-58, immunoprecipitated molecular complexes containing the NKR-P1 or CD94 molecules, respectively, by specific monoclonal antibodies, and performed in vitro kinase assays on the immunoprecipitates. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, autoradiography, and phospho-amino acid analysis revealed the presence of in vitro tyrosine phosphorylated proteins that were subsequently identified by re-precipitation (and/or by western blotting) as the respective C-type lectin molecules and Src family kinases Lck, Lyn, and Fyn. The NKR-P1 and the CD94-containing complexes were independent of each other and both very large, as judged by Sepharose 4B gel chromatography. Crosslinking of NKR-P1 on the cell surface induced transient in vivo tyrosine phosphorylation of cellular protein substrates. These results indicate involvement of the associated Src-family kinases in signaling via the NKR-P1 and CD94 receptors.

• MeSH
• antigeny povrchové metabolismus   MeSH
• buňky NK imunologie   MeSH
• CD antigeny metabolismus   MeSH
• fosforylace MeSH
• fosfotyrosin metabolismus   MeSH
• lektinové receptory NK-buněk - podrodina B MeSH
• lektinové receptory NK-buněk - podrodina D MeSH
• lektiny typu C * MeSH
• lidé MeSH
• makromolekulární látky MeSH
• membránové glykoproteiny metabolismus   MeSH
• molekulová hmotnost MeSH
• precipitinové testy MeSH
• receptory imunologické metabolismus   MeSH
• signální transdukce MeSH
• src homologní domény MeSH
• tyrosinkinasy metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Názvy látek
• antigeny povrchové MeSH
• CD antigeny MeSH
• fosfotyrosin MeSH
• KLRB1 protein, human MeSH Prohlížeč
• KLRD1 protein, human MeSH Prohlížeč
• lektinové receptory NK-buněk - podrodina B MeSH
• lektinové receptory NK-buněk - podrodina D MeSH
• lektiny typu C * MeSH
• makromolekulární látky MeSH
• membránové glykoproteiny MeSH
• receptory imunologické MeSH
• tyrosinkinasy MeSH