Cell-surface expression and alloantigenic function of a human nonclassical class I molecule (HLA-E) in transgenic mice.
We have introduced the gene (E*01033) encoding the heavy chain of the human nonclassical MHC class I Ag, HLA-E, into the mouse genome. Two founder mice carry a 21-kb fragment, the others bear an 8-kb fragment. Each of the founder mice was mated to mice of an already established C57BL/10 transgenic line expressing human beta2-microglobulin (beta2m). Cell surface HLA-E was detected on lymph node cells by flow cytometry only in the presence of endogenous human beta2m. However, HLA-E-reactive mouse CTL (H-2-unrestricted) lysed efficiently the target cells originating from HLA-E transgenic mice without human beta2m, showing that the HLA-E protein can be transported to the cell surface in the absence of human beta2m, presumably by association with murine beta2m. Rejection of skin grafts from HLA-E transgenic mice demonstrates that HLA-E behaves as a transplantation Ag in mice. HLA-E transgenic spleen cells are effective in stimulating an allogeneic CTL response in normal and human classical class I (HLA-B27) transgenic mice. Furthermore, results from split-well analysis indicate that the majority of the primary in vivo-induced CTL recognizes HLA-E as an intact molecule (H-2-unrestricted recognition) and not as an HLA-E-derived peptide presented by a mouse MHC molecule, although a small fraction (ranging from 4 to 21%) of the primary in vivo-induced CTL is able to recognize HLA-E in an H-2-restricted manner. Based on these observations, we conclude that HLA-E exhibits alloantigenic properties that are indistinguishable from classical HLA class I molecules when expressed in transgenic mice.
Pacasova
R
R
Mouse Immunogenetics, U462, Institut National de la Santé et de la Recherche Médicale, Saint-Louis Hospital, Paris, France.
Martinozzi
S
S
Boulouis
H J
HJ
Ulbrecht
M
M
Vieville
J C
JC
Sigaux
F
F
Weiss
E H
EH
Pla
M
M
D000818:Animals; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000138:chemical synthesis / Q000276:immunology; D006680:HLA Antigens / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology; D015796:HLA-B27 Antigen / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007519:Isoantigens / Q000235:genetics / Q000502:physiology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000276:immunology*; D016038:Skin Transplantation / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019076:Transgenes / Q000276:immunology; D001613:beta 2-Microglobulin / Q000502:physiology; D000097625:HLA-E Antigens
D006680:HLA Antigens; D015796:HLA-B27 Antigen; D015395:Histocompatibility Antigens Class I; D007519:Isoantigens; D001613:beta 2-Microglobulin; D000097625:HLA-E Antigens