NK Cells from Human MHC Class I (HLA-B) Transgenic Mice Do Not Mediate Hybrid Resistance Killing Against Parental Nontransgenic cells

We have investigated the capacity of human MHC class I HLA-B gene products, HLA-B27, -B7 (fully human), and -B7kb (human-mouse hybrid consisting of the alpha1 and alpha2 domains of HLA-B7, and the alpha3 and cytoplasmic domains of mouse H-2Kb), expressed on mouse NK cells during ontogeny to influenc...

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Bibliographic Details
Published in:The Journal of immunology (1950) 1998-01, Vol.160 (2), p.674-680
Main Authors: Kung, Sam K. P, Su, Ruey-Chyi, Graham, Jeremy J. K, Chamberlain, John W, Miller, Richard G
Format: Article
Language:English
Subjects:
Animals
Cell Line
Concanavalin A - pharmacology
Crosses, Genetic
Cytotoxicity, Immunologic - genetics
Female
H-2 Antigens - biosynthesis
Histocompatibility Antigens Class I - genetics
Histocompatibility Antigens Class I - immunology
HLA-B Antigens - biosynthesis
HLA-B Antigens - genetics
HLA-B Antigens - immunology
HLA-B27 Antigen - immunology
HLA-B27 Antigen - metabolism
Humans
Immunity, Innate - genetics
Killer Cells, Natural - immunology
Lymphocyte Activation
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic - immunology
Peptides - immunology
Peptides - metabolism
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Summary:We have investigated the capacity of human MHC class I HLA-B gene products, HLA-B27, -B7 (fully human), and -B7kb (human-mouse hybrid consisting of the alpha1 and alpha2 domains of HLA-B7, and the alpha3 and cytoplasmic domains of mouse H-2Kb), expressed on mouse NK cells during ontogeny to influence NK recognition of otherwise syngeneic mouse target cells. Despite a high level of surface expression of the transgene (comparable to that of endogeneous H-2DbKb molecules), the direct killing of YAC-1 targets, and the killing of P815 targets in a redirected lysis assay, the NK effectors of these transgenic mice could not mediate hybrid resistance-like killing of nontransgenic C57BL/6 target cells either in vitro or in vivo. Splenocytes from B6-B27 mice could be used to generate CTL lines against a B27-binding peptide, implying that T cells restricted by HLA-B27 developed during ontogeny. NK cells from B6-B27 could lyse B6-B27 Con A lymphoblasts pulsed with Db-binding peptide but not B27-binding peptides. Taken together, our results show that these human HLA-B transgene products cannot function as class I MHC "self" elements for mouse NK cells, even when present throughout ontogeny.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.160.2.674