Development of intra-natural killer complex (NKC) recombinant and congenic mouse strains for mapping and functional analysis of NK cell regulatory loci

Natural killer (NK) cells play an important role in limiting the acute phase of replication of certain infectious agents and in restricting tumor cell proliferation. In mice the NK complex (NKC) represents a critical genomic region that regulates NK cell function. Located on the distal region of chr...

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Bibliographic Details
Published in:Immunogenetics (New York) 1999-03, Vol.49 (3), p.238-241
Main Authors: Scalzo, A A, Brown, M G, Chu, D T, Heusel, J W, Yokoyama, W M, Forbes, C A
Format: Article
Language:English
Subjects:
AIDS/HIV
Animals
Cd69 gene
Cd94 gene
chromosome 12
chromosome 4
chromosome 6
Chromosome Mapping
Crosses, Genetic
Cytomegalovirus - immunology
Cytomegalovirus Infections - genetics
Cytomegalovirus Infections - immunology
Cytomegalovirus Infections - virology
Female
Genes
Genotype
Immunity, Innate - genetics
Killer Cells, Natural - immunology
Killer Cells, Natural - metabolism
Ly-49 gene
Ly-55 gene
Male
Mice
Mice, Congenic
Mice, Inbred BALB C
NK1.1 antigen
Nkg2d gene
Nkrp1 gene
Phenotype
Recombination, Genetic
Spleen - virology
Viral Load
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Summary:Natural killer (NK) cells play an important role in limiting the acute phase of replication of certain infectious agents and in restricting tumor cell proliferation. In mice the NK complex (NKC) represents a critical genomic region that regulates NK cell function. Located on the distal region of chromosome 6, the NKC is >2 megabases (Mb) and is comprised of several multigene families and individual genes. These encode NK receptors that regulate activation and inhibition of NK cells and include the Ly55 (Nkrp1) and Ly49 multigene families, together with the Cd69, Cd94, and Nkg2d genes. Homologous NKC regions have also been defined on chromosome 4 in the rat and on chromosome 12p13 in humans. It is noteworthy that to date no Ly49 orthologues have been found in the human NKC. All NKC genes studied so far encode type II integral membrane proteins with C-lectin domains and are either homodimeric (mNKR-P1, CD69, and Ly49) or heterodimeric (i.e., CD94 with various members of the NKG2 family). The NK1.1 alloantigen, which is encoded by Ly55-c (Nkrp1-c), is an activation receptor on NK cells that has specificity for illdefined carbohydrate moieties on target cells. Ly49 family members have distinct specificities for target cell class I major histocompatibility complex (MHC) molecules, and depending on the presence or absence of immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in their cytoplasmic domain will function as inhibition or activation receptors for NK cells, respectively.
ISSN:0093-7711
1432-1211
DOI:10.1007/s002510050486