Altered natural killer cell repertoire in Tap-1 mutant mice.
We have analyzed the specificity and function of natural killer (NK) cells in mice with a homozygous deletion of the major histocompatibility complex (MHC)-encoded transporter gene associated with MHC class I-restricted antigen presentation (Tap-1). These mice express very low levels of class I molecules at the cell surface, and these molecules are either devoid of peptide or occupied only by TAP-independent peptides. NK cells in Tap-1 -/- mice, through normal in number, appeared tolerant toward autologous Tap-1 -/- Con A-activated blasts, Tap-1 -/- as well as allogeneic BALB/c bone marrow cells, and RMA-S tumor cell grafts. In contrast, they killed YAC-1 cells as efficiently as did NK cells from wild-type mice. Defective Tap-1 expression was sufficient to render nontransformed target cells sensitive to NK cell-mediated lysis. It is concluded that proper expression of TAP molecules is necessary for normal development of NK cells, as well as for rendering target cells resistant to NK cell-mediated lysis. These results support the hypothesis that class I molecules of the MHC influence the sensitivity of target cells to lysis by NK cells, as well as the development of the NK cell repertoire.
Ljunggren
H G
HG
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden.
Van Kaer
L
L
Ploegh
H L
HL
Tonegawa
S
S
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D005805:Genes, MHC Class I; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006720:Homozygote; D007694:Killer Cells, Natural / Q000276:immunology*; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009368:Neoplasm Transplantation / Q000276:immunology*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; D015395:Histocompatibility Antigens Class I; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse