Variable MHC class I engagement by Ly49 natural killer cell receptors demonstrated by the crystal structure of Ly49C bound to H-2Kb

Julie Dam, Rongjin Guan, Kannan Natarajan, Nazzareno Dimasi, Lukasz K. Chlewicki, David M. Kranz, Peter Schuck, David H. Margulies, Roy A. Mariuzza

Research output: Contribution to journalArticlepeer-review

Abstract

The Ly49 family of natural killer (NK) receptors regulates NK cell function by sensing major histocompatibility complex (MHC) class I. Ly49 receptors show complex patterns of MHC class I cross-reactivity and, in certain cases, peptide selectivity. To investigate whether specificity differences result from topological differences in MHC class I engagement, we determined the structure of the peptide-selective receptor Ly49C in complex with H-2Kb. The Ly49C homodimer binds two MHC class I molecules in symmetrical way, a mode distinct from that of Ly49A, which binds MHC class I asymmetrically. Ly49C does not directly contact the MHC-bound peptide. In addition, MHC crosslinking by Ly49C was demonstrated in solution. We propose a dynamic model for Ly49-MHC class I interactions involving conformational changes in the receptor, whereby variations in Ly49 dimerization mediate different MHC-binding modes.

Original languageEnglish (US)
Pages (from-to)1213-1222
Number of pages10
JournalNature Immunology
Volume4
Issue number12
DOIs
StatePublished - Dec 2003

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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