Functional consequences of interactions between human NKR-P1A and its ligand LLT1 expressed on activated dendritic cells and B cells.
Lectin-like transcript-1 (LLT1) (also named osteoclast inhibitory lectin or CLEC2D) is a ligand for the human NKR-P1A (CD161) receptor, present on NK cells and T cells. To further understand the physiological relevance of this interaction, we developed mAbs against LLT1, characterized the expression pattern of LLT1, and explored the functional consequence of LLT1 engagement of the NKR-P1A receptor on NK cells and T cells. LLT1 is expressed on TLR-activated plasmacytoid dendritic, TLR-activated monocyte-derived dendritic cells, and on B cells stimulated through TLR9, surface Ig, or CD40. Interactions between NKR-P1A on NK cells and LLT1 on target cells inhibit NK cell-mediated cytotoxicity and cytokine production and can inhibit TNF-alpha production by TCR-activated NKR-P1A(+) CD8(+) T cells. In contrast, NKR-P1A failed to inhibit or augment the TCR-dependent activation of NKR-P1A-bearing CD4(+) T cells. Expression of LLT1 on activated dendritic cells and B cells suggests that it might regulate the cross-talk between NK cells and APCs.
Rosen
David B
DB
Department of Microbiology and Immunology, Biomedical Sciences Graduate Program, and Cancer Research Institute, University of California, San Francisco, CA 94143, USA.
Cao
Wei
W
Avery
Danielle T
DT
Tangye
Stuart G
SG
Liu
Yong-Jun
YJ
Houchins
J P
JP
Lanier
Lewis L
LL
D000954:Antigens, Surface / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000502:physiology; D003713:Dendritic Cells / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006801:Humans; D007156:Immunologic Memory / Q000502:physiology; D007694:Killer Cells, Natural / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism*; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D055651:NK Cell Lectin-Like Receptor Subfamily B; D020411:Oligonucleotide Array Sequence Analysis; D020239:Receptor Cross-Talk / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism
D000954:Antigens, Surface; C400041:CLEC2D protein, human; C527203:KLRB1 protein, human; D037181:Lectins, C-Type; D008024:Ligands; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors