Alloreactive immune responses of transgenic mice expressing a foreign transplantation antigen in a soluble form.
Transfection of cells with the H-2Kk gene lacking the transmembrane and cytoplasmic segments resulted in secretion of the H-2Kk protein, as determined by immunoprecipitation with monoclonal anti-H-2Kk antibodies. Transgenic (H-2b X H-2d)F1 mice were established carrying integrated copies of the modified H-2Kk gene. Expression of the soluble H-2Kk antigen in the transgenic mice was demonstrated in cell supernatants of biosynthetically labeled splenic and thymic Con A blasts as well as bone marrow-derived macrophages. Soluble H-2Kk molecules were also present in the sera of the transgenic animals. No cell-surface expression of the H-2Kk antigen could be observed. In spite of the presence of the soluble H-2Kk molecules in the transgenic mice, the animals were able to generate H-2Kk-specific cytolytic T cells as well as antibody responses when stimulated with cell-surface-bound H-2Kk antigens. These responses were indistinguishable from those of the nontransgenic littermates. Possible explanations for the observed lack of tolerance are discussed.
Arnold
B
B
Institute for Immunology and Genetics, German Cancer Research Center, Heidelberg.
Dill
O
O
Küblbeck
G
G
Jatsch
L
L
Simon
M M
MM
Tucker
J
J
Hämmerling
G J
GJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D007108:Immune Tolerance; D007518:Isoantibodies / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000276:immunology; D008811:Mice, Inbred DBA / Q000276:immunology; D008822:Mice, Transgenic / Q000276:immunology; D012995:Solubility; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000911:Antibodies, Monoclonal; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D007518:Isoantibodies