Mapping the ligand of the NK inhibitory receptor Ly49A on living cells

Hyun Chung Doo Hyun Chung, K. Natarajan, L. F. Boyd, J. Tormo, R. A. Mariuzza, W. M. Yokoyama, D. H. Margulies

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30 Scopus citations

Abstract

We have used a recombinant, biotinylated form of the mouse NK cell inhibitory receptor, Ly49A, to visualize the expression of MHC class I (MHC-I) ligands on living lymphoid cells. A panel of murine strains, including MHC congenic lines, was examined. We detected binding of Ly49A to cells expressing H-2D(d), H-2D(k), and H-2D(p) but not to those expressing other MHC molecules. Cells of the MHC-recombinant strain B10.PL (H-2(u)) not only bound Ly49A but also inhibited cytolysis by Ly49A+ effector cells, consistent with the correlation of in vitro binding and NK cell function. Binding of Ly49A to H-2D(d)-bearing cells of different lymphoid tissues was proportional to the level of H-2D(d) expression and was not related to the lineage of the cells examined. These binding results, interpreted in the context of amino acid sequence comparisons and the recently determined three-dimensional structure of the Ly49A/H-2D(d) complex, suggest a role for amino acid residues at the amino-terminal end of the α1 helix of the MHC-I molecule for Ly49A interaction. This view is supported by a marked decrease in affinity of an H-2D(d) mutant, I52 M, for Ly49A. Thus, allelic variation of MHC-I molecules controls measurable affinity for the NK inhibitory receptor Ly49A and explains differences in functional recognition in different mouse strains.

Original languageEnglish
Pages (from-to)6922-6932
Number of pages11
JournalJournal of Immunology
Volume165
Issue number12
StatePublished - Dec 15 2000
Externally publishedYes

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    Doo Hyun Chung, H. C., Natarajan, K., Boyd, L. F., Tormo, J., Mariuzza, R. A., Yokoyama, W. M., & Margulies, D. H. (2000). Mapping the ligand of the NK inhibitory receptor Ly49A on living cells. Journal of Immunology, 165(12), 6922-6932.