Tumorigenicity conferred to lymphoma mutant by major histocompatibility complex-encoded transporter gene.
Presentation of antigenic peptides by major histocompatibility complex (MHC) class I molecules requires MHC-encoded molecules of the adenosine triphosphate binding cassette (ABC) family. Defects in these proteins represent a potential risk, since they are essential links in the machinery of T cell-mediated surveillance which continuously scrutinizes peptide samples of cellular proteins. Nevertheless, transfection of the mouse lymphoma mutant RMA-S with the rat ABC gene mtp2a (homologue to mouse HAM2 and human RING11), commonly termed TAP-2 genes, led to a marked increase in tumor outgrowth potential in vivo. This occurred despite restored antigen presentation and sensitivity to cytotoxic T lymphocytes, and was found to be due to escape from natural killer (NK) cell-mediated rejection. It has previously been proposed that adequate expression of self-MHC class I is one important mechanism to avoid elimination by NK cells. Our data argue that a defect in the machinery responsible for processing and loading of peptides into MHC class I molecules is sufficient to render cells sensitive to elimination by NK cells. The latter thus appear to function as a surveillance of the peptide surveillance machinery.
Franksson
L
L
Department of Tumor Biology, Karolinska Institutet, Stockholm, Sweden.
George
E
E
Powis
S
S
Butcher
G
G
Howard
J
J
Kärre
K
K
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D007694:Killer Cells, Natural / Q000276:immunology; D008223:Lymphoma / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D008285:Major Histocompatibility Complex; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D014162:Transfection
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; D000949:Histocompatibility Antigens Class II; C489516:Tap2 protein, mouse; C489514:Tap2 protein, rat; C071692:TAP2 protein, human