Abstract:
:The "NK-triggering-antigen regulator" (Nktar) gene is a locus identified in the C57BL/6 genome which regulates the ability of unlabeled activated Con A blasts to compete for recognition of labeled syngeneic Con A blasts by BALB/c NK cells. Linkage analysis on Con A blasts from (BALB/c x CByB6F1) N2 backcross progeny for (1) relative level of competitive inhibition of BALB/c NK lysis of syngeneic Con A blasts and (2) genotypes at polymorphic microsatellite markers distributed throughout the mouse genome mapped the Nktar gene locus to a 5-cM region of chromosome 10 containing the interferon-gamma receptor (Ifngr) gene locus. N2 Con A blasts exhibited an inverse relationship between (a) their cell surface density of IFN-gammaR molecules detected by FACS with monoclonal anti-CD119 and (b) their cold target inhibition of BALB/c NK self-reactivity. Con A blasts from Ifngr(-/-) knockout mice showed a relatively high level of inhibition of BALB/c NK self-lysis and a relatively low level of class I MHC, which were both reversed by transient transfection with the Ifngr gene. Sequencing studies showed that Balb/c Ifngr encodes a Gly(69) whereas C57BL/6 Ifngr encodes Glu(69) due to a difference at nucleotide 284. Sequencing studies of N2 progeny demonstrated 100% concordance between their Nktar inhibitory phenotype and their Ifngr genotype. These findings demonstrate that the Nktar and Ifngr loci are identical. They further indicate that polymorphisms related to the Ifngr locus and affecting expression of cell surface IFN-gammaR may underlie genetic differences in the availability of NK-triggering antigens (NKTAgs) to recognition by self-reactive BALB/c NK cells by differentially affecting the ability of IFN-gammaR molecules to mediate up-regulation of NKTAg-masking class I molecules.
journal_name
Cell Immunoljournal_title
Cellular immunologyauthors
Chou SR,Brownell A,Ko MS,Kaplan Jdoi
10.1006/cimm.1999.1624subject
Has Abstractpub_date
2000-03-15 00:00:00pages
88-97issue
2eissn
0008-8749issn
1090-2163pii
S0008-8749(99)91624-6journal_volume
200pub_type
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journal_title:Cellular immunology
pub_type: 杂志文章
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更新日期:1984-05-01 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章
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journal_title:Cellular immunology
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