Rejection of allogeneic and syngeneic but not MHC class I-deficient tumor grafts by MHC class I-deficient mice.
The ability of TAP1-/-, beta2m-/-, and TAP1/beta2m-/- mice to mount rejection responses against allogeneic, syngeneic, and MHC class I-deficient tumor grafts was examined. The results demonstrate a potent ability of TAP1-/- and beta2m-/- as well as TAP1/beta2m-/- mice to reject allogeneic tumors. In contrast to published data, rejection of syngeneic MHC class I-expressing tumors was also observed. This response was specific for the MHC class I-deficient mice, since wild-type mice did not reject syngeneic MHC class I-positive tumors under identical experimental conditions. The rejection response of syngeneic tumors required preimmunization of the mice and was MHC class I specific at the level of priming as well as at the level of the tumor target. Finally, MHC class I-deficient tumor grafts were accepted in MHC class I-deficient mice while similar grafts were rejected in wild-type mice. In summary, while MHC class I-deficient mice have retained a capacity to reject allogeneic tumors. they have gained an ability to reject syngeneic MHC class I-positive tumors and lost the ability to reject MHC class I-negative tumors. The present results are discussed in relation to the role of MHC class I molecules in selecting functional CD8+ T and NK cell repertoires, and the development of cell-mediated immunity.
Freland
S
S
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
Chambers
B J
BJ
Andersson
M
M
Van Kaer
L
L
Ljunggren
H G
HG
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D006084:Graft Rejection / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics*; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000276:immunology; D012515:Mast-Cell Sarcoma / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009368:Neoplasm Transplantation / Q000276:immunology*; D012513:Sarcoma, Experimental / Q000235:genetics / Q000276:immunology; D013045:Species Specificity; D014184:Transplantation, Homologous / Q000276:immunology*; D014185:Transplantation, Isogeneic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; D001613:beta 2-Microglobulin