Regulation of cytotoxic T lymphocyte triggering by PIR-B on dendritic cells.
Priming of cytotoxic T lymphocytes (CTLs) by dendritic cells (DCs) is crucial for elimination of pathogens and malignant cells. To activate CTLs, DCs present antigenic peptide-complexed MHC class I molecules (MHC-I) that will be recognized by the CTLs with T cell receptors and CD8 molecules. Here we show that paired Ig-like receptor (PIR)-B, an MHC-I receptor expressed on antigen-presenting cells, can regulate CTL triggering by blocking the access of CD8 molecules to MHC-I. PIR-B-deficient DCs evoked CTLs more efficiently, leading to accelerated graft and tumor rejection. PIR-B(+) non-DC transfectant cells served as less efficient stimulators and targets for CTLs than PIR-B(-) cells at the effector phase in vitro. On surface plasmon resonance analysis, PIR-B and CD8alpha alpha were revealed to compete in binding to MHC-I. Our results may provide a novel strategy for regulating CTL-mediated immunity and diseases in a sterical manner.
Endo
Shota
S
Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.
Sakamoto
Yuzuru
Y
Kobayashi
Eiji
E
Nakamura
Akira
A
Takai
Toshiyuki
T
D000818:Animals; D017951:Antigen Presentation; D016827:CD8 Antigens / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016038:Skin Transplantation / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection
D016827:CD8 Antigens; D016207:Cytokines; D006183:H-2 Antigens; C105949:Pirb protein, mouse; D011971:Receptors, Immunologic
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