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 journalArticle

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 1 2003

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Natural Killer Cell Receptors
Major Histocompatibility Complex
Peptides
Peptide Receptors
Dimerization

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Variable MHC class I engagement by Ly49 natural killer cell receptors demonstrated by the crystal structure of Ly49C bound to H-2Kb. / Dam, Julie; Guan, Rongjin; Natarajan, Kannan; Dimasi, Nazzareno; Chlewicki, Lukasz K.; Kranz, David M; Schuck, Peter; Margulies, David H.; Mariuzza, Roy A.

In: Nature Immunology, Vol. 4, No. 12, 01.12.2003, p. 1213-1222.

Research output: Contribution to journalArticle

Dam, J, Guan, R, Natarajan, K, Dimasi, N, Chlewicki, LK, Kranz, DM, Schuck, P, Margulies, DH & Mariuzza, RA 2003, 'Variable MHC class I engagement by Ly49 natural killer cell receptors demonstrated by the crystal structure of Ly49C bound to H-2Kb', Nature Immunology, vol. 4, no. 12, pp. 1213-1222. https://doi.org/10.1038/ni1006
Dam, Julie ; Guan, Rongjin ; Natarajan, Kannan ; Dimasi, Nazzareno ; Chlewicki, Lukasz K. ; Kranz, David M ; Schuck, Peter ; Margulies, David H. ; Mariuzza, Roy A. / Variable MHC class I engagement by Ly49 natural killer cell receptors demonstrated by the crystal structure of Ly49C bound to H-2Kb. In: Nature Immunology. 2003 ; Vol. 4, No. 12. pp. 1213-1222.
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