Evidence of functional Cd94 polymorphism in a free-living house mouse population
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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.
KeywordsNK cell Inhibitory/activating receptors MHC Comparative immunology/evolution Genomics
- M. m.
Natural killer gene complex
Qa-1 determinant modifier
Killer cell immunoglobulin-like receptor
LEK, ED, AKS, and PB conceived the study and designed the experiments. LEK, ED, and PB wrote the manuscript, with contributions from JP and AKS. LEK, JP, and PB caught wild mice. LEK, ED, EGB, PCS, and PB performed lab experiments and analyses. The authors thank Stine Braaen, Hanne M. Haatveit, and Grethe M. Johansen at the Norwegian University of Life Sciences for technical assistance.
This work was funded internally at NMBU.
Compliance with ethical standards
Conflict of interest
The authors declare no financial or commercial conflicts of interest to the content of this article.
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