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 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.
Kung
S K
SK
Department of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Canada.
Su
R C
RC
Graham
J J
JJ
Chamberlain
J W
JW
Miller
R G
RG
D000818:Animals; D002460:Cell Line; D003208:Concanavalin A / Q000494:pharmacology; D003433:Crosses, Genetic; D003602:Cytotoxicity, Immunologic / Q000235:genetics*; D005260:Female; D006183:H-2 Antigens / Q000096:biosynthesis; D015235:HLA-B Antigens / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D015796:HLA-B27 Antigen / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000276:immunology*; D010455:Peptides / Q000276:immunology / Q000378:metabolism
D006183:H-2 Antigens; C024755:H-2K(K) antigen; D015235:HLA-B Antigens; D015796:HLA-B27 Antigen; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D003208:Concanavalin A