The functional binding site for the C-type lectin-like natural killer cell receptor Ly49A spans three domains of its major histocompatibility complex class I ligand

Naoki Matsumoto, Motoaki Mitsuki, Kyoko Tajima, Wayne M. Yokoyama, Kazuo Yamamoto

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

Abstract

Natural killer (NK) cells express receptors that recognize major histocompatibility complex (MHC) class I molecules and regulate cytotoxicity of target cells. In this study, we demonstrate that Ly49A, a prototypical C-type lectin-like receptor expressed on mouse NK cells, requires species-specific determinants on β2-microglobulin (β2m) to recognize its mouse MHC class I ligand, H-2Dd. The involvement of β2m in the interaction between Ly49A and H-2Dd is also demonstrated by the functional effects of a β2m-specific antibody. We also define three residues in α1/α2 and α3 domains of H-2Dd that are critical for the recognition of H-2Dd on target cells by Ly49A. In the crystal structure of the Ly49A/H-2Dd complex, these residues are involved in hydrogen bonding to Ly49A in one of the two potential Ly49A binding sites on H-2Dd. These data unambiguously indicate that the functional effect of Ly49A as an MHC class I-specific NK cell receptor is mediated by binding to a concave region formed by three structural domains of H-2Dd, which partially overlaps the CD8 binding site.

Original languageEnglish
Pages (from-to)147-157
Number of pages11
JournalJournal of Experimental Medicine
Volume193
Issue number2
DOIs
StatePublished - Jan 15 2001

Keywords

  • Cytotoxicity
  • H-2 antigens
  • Inhibitory receptor
  • Mutation
  • β2-Microglobulin

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