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

Eishi Baba, Robert Erskine, Jonathan E. Boyson, George B. Cohen, Daniel M. Davis, Pratap Malik, Ofer Mandelboim, Hugh T. Reyburn, Jack L. Strominger*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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 nonglycosylated 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.

Original languageAmerican English
Pages (from-to)1202-1218
Number of pages17
JournalHuman Immunology
Volume61
Issue number12
DOIs
StatePublished - 2000

Bibliographical note

Funding Information:
This work was supported by a National Institutes of Health research grant (R35-CA47554); a postdoctoral fellowship from The Irvington Institute for Immunological Research, New York to D.M. Davis; and the Cancer Research Fund of The Damon Runyon-Walter Winchell Foundation Fellowship grant No. DRG1454 to O. Mandelboim.

Keywords

  • Carbohydrate
  • Inhibitory receptor
  • MHC
  • NK cells

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