Altered natural killer cell repertoire in Tap-1 mutant mice.

Ljunggren HG, Van Kaer L, Ploegh HL, Tonegawa S
Proc Natl Acad Sci U S A. 1994 91 (14): 6520-4

PMID: 8022815 · PMCID: PMC44234 · DOI:10.1073/pnas.91.14.6520

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.

MeSH Terms (18)

Animals ATP-Binding Cassette Transporters ATP Binding Cassette Transporter, Subfamily B, Member 2 Bone Marrow Transplantation Carrier Proteins Cell Line Cytotoxicity, Immunologic Flow Cytometry Genes, MHC Class I Histocompatibility Antigens Class I Homozygote Killer Cells, Natural Major Histocompatibility Complex Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Mutant Strains Neoplasm Transplantation

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