Molecular and genetic basis for strain-dependent NK1.1 alloreactivity of mouse NK cells.
NK1.1 alloantigen expression can be used to define NK cells in certain mouse strains, such as B6 (NKR-P1C) and SJL (NKR-P1B). However, BALB/c NK cells do not react with the anti-NK1.1 mAb, PK136. To investigate the NK1.1(-) phenotype of BALB/c NK cells, we have undertaken NK1.1 epitope mapping and genomic analysis of the BALB/c Nkrp1 region. Bacterial artificial chromosome library analysis reveals that, unlike the Ly49 region, the Nkrp1-Ocil/Clr region displays limited genetic divergence between B6 and BALB/c mice. In fact, significant divergence is confined to the Nkrp1b and Nkrp1c genes. Strikingly, the B6 Nkrp1d gene appears to represent a divergent allele of the Nkrp1b gene in BALB/c mice and other strains. Importantly, BALB/c NK cells express abundant and functional Nkrp1 transcripts, and the BALB/c NKR-P1B receptor functionally binds Ocil/Clr-b ligand. However, the BALB/c NKR-P1B/C sequences differ from those of the known NK1.1 alloantigens, and epitope mapping demonstrates that directed mutation of a single amino acid in the NKR-P1B(BALB) protein confers NK1.1 reactivity. Thus, PK136 mAb recognizes, in part, a distal C-terminal epitope present in NKR-P1B(Sw/SJL) and NKR-P1C(B6), but absent in NKR-P1A/D/F(B6) and NKR-P1B/C(BALB). Allelic divergence of the Nkrp1b/c gene products and limited divergence of the BALB/c Nkrp1-Ocil/Clr region explain a longstanding confusion regarding the strain-specific NK1.1 alloantigen reactivity of mouse NK cells.
Carlyle
James R
JR
Department of Immunology, University of Toronto, Sunnybrook and Women's Research Institute, ON, Canada. james.caryle@utoronto.ca
Mesci
Aruz
A
Ljutic
Belma
B
Belanger
Simon
S
Tai
Lee-Hwa
LH
Rousselle
Etienne
E
Troke
Angela D
AD
Proteau
Marie-France
MF
Makrigiannis
Andrew P
AP
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000950:Antigens, Ly; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000235:genetics*; D002460:Cell Line; D015723:Gene Library; D023061:Gene Order; D006239:Haplotypes; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D037181:Lectins, C-Type / Q000096:biosynthesis* / Q000235:genetics*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008969:Molecular Sequence Data; D005810:Multigene Family; D016254:Mutagenesis, Insertional; D055651:NK Cell Lectin-Like Receptor Subfamily B; D020161:Physical Chromosome Mapping; D013045:Species Specificity
D000950:Antigens, Ly; D000954:Antigens, Surface; C527203:KLRB1 protein, human; C527212:Klrb1b protein, mouse; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D008565:Membrane Proteins; D055651:NK Cell Lectin-Like Receptor Subfamily B; C429003:Ocil protein, mouse