Tumor cells of non-hematopoietic and hematopoietic origins express activation-induced C-type lectin, the ligand for killer cell lectin-like receptor F1.
Killer cell lectin-like receptor F1 (KLRF1) is an activating C-type lectin-like receptor expressed on human NK cells and subsets of T cells. In this study, we show that activation-induced C-type lectin (AICL) is a unique KLRF1 ligand expressed on tumor cell lines of hematopoietic and non-hematopoietic origins. We screened a panel of human tumor cell lines using the KLRF1 reporter cells and found that several tumor lines expressed KLRF1 ligands. We characterized a putative KLRF1 ligand expressed on the U937 cell line. The molecular mass for the deglycosylated ligand was 28 kDa under non-reducing condition and 17 kDa under reducing condition, suggesting that the KLRF1 ligand is a homodimer. By expression cloning from a U937 cDNA library, we identified AICL as a KLRF1 ligand. We generated mAbs against AICL to identify the KLRF1 ligands on non-hematopoietic tumor lines. The anti-AICL mAbs stained the tumor lines that express the KLRF1 ligands and importantly the interaction of KLRF1 with the KLRF1 ligand on non-hematopoietic tumors was completely blocked by the two anti-AICL mAbs. Moreover, NK cell degranulation triggered by AICL-expressing targets was partially inhibited by the anti-AICL mAb. Finally, we demonstrate that AICL is expressed in human primary liver cancers. These results suggest that AICL is expressed on tumor cells of non-hematopoietic origins and raise the possibility that AICL may contribute to NK cell surveillance of tumor cells.
Akatsuka
Akinobu
A
Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8562, Japan.
Ito
Masayuki
M
Yamauchi
Chisako
C
Ochiai
Atsushi
A
Yamamoto
Kazuo
K
Matsumoto
Naoki
N
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015550:Cell Degranulation / Q000187:drug effects; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D005260:Female; D006410:Hematopoiesis; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000187:drug effects; D055607:Receptors, Natural Killer Cell / Q000276:immunology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics
D000911:Antibodies, Monoclonal; C104778:CLEC2B protein, human; D007141:Immunoglobulin Fc Fragments; C431711:KLRF1 protein, human; D037181:Lectins, C-Type; D008024:Ligands; D008562:Membrane Glycoproteins; D055607:Receptors, Natural Killer Cell; D011993:Recombinant Fusion Proteins