Branched I antigens on leukemia cells enhanced sensitivity against natural killer-cell cytotoxicity through affecting the target-effector interaction.
The aberrant glycosylation on proteins and lipids has been implicated in malignant transformations for promoting the tumorigenesis, metastasis, and evasion from the host immunity. The I-branching β-1,6-N-acetylglucosaminyltransferase, converting the straight i to branched I histo-blood group antigens, reportedly could influence the migration, invasion, and metastasis of solid tumors.



We first chose the highly cytotoxic natural killer (NK)-92MI cells as effector against leukemia for this cell line has been used in several clinical trials. Fluorescence-activated cell sorting and nonradioactive cytotoxicity assay were performed to reexamine the role of NK-activating receptors, their corresponding ligands, and the tumor-associated carbohydrate antigens in this NK-92MI-leukemia in vitro system. The I role on cytotoxic mechanism was further studied especially on the effector-target interactions by cytotoxic analysis and conjugate formation assay.



We showed that expression levels of leukemia surface ligands for NK-activating receptors did not positively reflect susceptibility to NK-92MI. Instead, the expression of I antigen on the leukemia cells was found important in mediating the susceptibility to NK targeting by affecting the interaction with effector cells. Furthermore, susceptibility was shown to dramatically increase while overexpressing branched I antigens on the I- cells. By both conjugate and cytotoxicity assay, we revealed that the presence of I antigen on leukemia cells enhanced the interaction with NK-92MI cells, increasing susceptibility to cell-mediated lysis.



In our system, branched I antigens on the leukemia were involved in the immunosurveillance mediated by NK cells specifically through affecting the effector-target interaction.
Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.|Department of Medical Research, Mackay Memorial Hospital, New Taipei City, Taiwan.
Yen-Hua
YH
Lee
School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology.
Yi-Jen
YJ
Liao
Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.
Chin-Han
CH
Huang
Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.|The Center of Translational Medicine, Taipei Medical University, Taipei, Taiwan.
Fu-Ling
FL
Chang
Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.
Ting-Hsi
TH
Fan
Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.
Yuh-Ching
YC
Twu
D000951:Antigens, Neoplasm / Q000276:immunology*; D045744:Cell Line, Tumor; D006801:Humans; D007048:I Blood-Group System / Q000276:immunology*; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D007938:Leukemia / Q000276:immunology* / Q000473:pathology; D017351:N-Acetylglucosaminyltransferases / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology
D000951:Antigens, Neoplasm; D007048:I Blood-Group System; D009363:Neoplasm Proteins; C106501:N-acetylglucosaminyltransferase IGnT; D017351:N-Acetylglucosaminyltransferases