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N-linked carbohydrate on human leukocyte antigen-C and recognition by natural killer cell inhibitory receptors.

The possible role of carbohydrate in the interaction of HLA-C with a human inhibitory natural Killer cell Immunoglobulin-like Receptor with two Ig domains, KIR2DL1, was investigated. Transfectants of 721.221 (a class I MHC-negative human B cell line) expressing only HLA-Cw4 or -Cw6 or their respective non-glycosylated mutants (N86Q, S88A) were made. The binding of a KIR2DL1-Ig fusion protein to the non-glycosylated mutant HLA-Cw4- or -Cw6-expressing cells was markedly decreased compared to the wild type-expressing cells. The ability to induce an inhibitory signal in the NK tumor line YTS transfected with KIR2DL1 was also impaired in the nonglycosylated mutant expressing cells. Furthermore, in a second functional assay, mutant HLA-Cw4 and -Cw6 molecules had impaired ability to induce signal transduction in BW cells expressing a KIR2DL1-CD3 zeta chain chimeric protein. Thus, the deletion of the N-linked glycosylation signal in HLA-Cw4 and -Cw6 greatly reduced recognition by KIR2DL1. Alternative interpretations of the data are discussed.

Pubmed ID: 11163076

Authors

  • Baba E
  • Erskine R
  • Boyson JE
  • Cohen GB
  • Davis DM
  • Malik P
  • Mandelboim O
  • Reyburn HT
  • Strominger JL

Journal

Human immunology

Publication Data

December 22, 2000

Associated Grants

  • Agency: NCI NIH HHS, Id: R35-CA47554

Mesh Terms

  • Amino Acid Substitution
  • Animals
  • Antigens, CD
  • Asparagine
  • COS Cells
  • Carbohydrate Conformation
  • Carbohydrate Metabolism
  • Carbohydrates
  • Cell Line, Transformed
  • Cytotoxicity Tests, Immunologic
  • Cytotoxicity, Immunologic
  • Glutamine
  • Glycosylation
  • HLA-C Antigens
  • Humans
  • Immunoglobulins
  • Killer Cells, Natural
  • Lectins, C-Type
  • Membrane Glycoproteins
  • Mice
  • NK Cell Lectin-Like Receptor Subfamily D
  • Protein Binding
  • Receptors, Immunologic
  • Receptors, KIR
  • Receptors, KIR2DL1
  • Receptors, Natural Killer Cell
  • Recombinant Fusion Proteins
  • Signal Transduction
  • Swainsonine
  • Transfection
  • Tumor Cells, Cultured