Evidence of functional Cd94 polymorphism in a free-living house mouse population

Immunogenetics. 2019 Apr;71(4):321-333. doi: 10.1007/s00251-018-01100-x. Epub 2018 Dec 10.


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.

Keywords: Comparative immunology/evolution; Genomics; Inhibitory/activating receptors; MHC; NK cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • CD8-Positive T-Lymphocytes / metabolism*
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • HEK293 Cells
  • Histocompatibility Antigens Class I / chemistry
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Killer Cells, Natural / metabolism*
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • NK Cell Lectin-Like Receptor Subfamily C / chemistry
  • NK Cell Lectin-Like Receptor Subfamily C / genetics
  • NK Cell Lectin-Like Receptor Subfamily C / metabolism*
  • NK Cell Lectin-Like Receptor Subfamily D / chemistry
  • NK Cell Lectin-Like Receptor Subfamily D / genetics*
  • NK Cell Lectin-Like Receptor Subfamily D / metabolism
  • Norway
  • Peptides / chemistry
  • Peptides / genetics
  • Peptides / metabolism
  • Polymorphism, Genetic*
  • Protein Binding
  • Protein Multimerization
  • Sequence Homology, Amino Acid
  • Species Specificity


  • Histocompatibility Antigens Class I
  • NK Cell Lectin-Like Receptor Subfamily C
  • NK Cell Lectin-Like Receptor Subfamily D
  • Peptides
  • Q surface antigens
  • Qdm protein, mouse