Branched I antigens on leukemia cells enhanced sensitivity against natural killer–cell cytotoxicity through affecting the target–effector interaction

Yen Hua Lee, Yi Jen Liao, Chin Han Huang, Fu Ling Chang, Ting Hsi Fan, Yuh Ching Twu

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BACKGROUND: 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. STUDY DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Original languageEnglish
Pages (from-to)1040-1051
Number of pages12
Issue number4
Publication statusPublished - Apr 1 2017


ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology

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