A novel system of polymorphic and diverse NK cell receptors in primates

PLoS Genet. 2009 Oct;5(10):e1000688. doi: 10.1371/journal.pgen.1000688. Epub 2009 Oct 16.

Abstract

There are two main classes of natural killer (NK) cell receptors in mammals, the killer cell immunoglobulin-like receptors (KIR) and the structurally unrelated killer cell lectin-like receptors (KLR). While KIR represent the most diverse group of NK receptors in all primates studied to date, including humans, apes, and Old and New World monkeys, KLR represent the functional equivalent in rodents. Here, we report a first digression from this rule in lemurs, where the KLR (CD94/NKG2) rather than KIR constitute the most diverse group of NK cell receptors. We demonstrate that natural selection contributed to such diversification in lemurs and particularly targeted KLR residues interacting with the peptide presented by MHC class I ligands. We further show that lemurs lack a strict ortholog or functional equivalent of MHC-E, the ligands of non-polymorphic KLR in "higher" primates. Our data support the existence of a hitherto unknown system of polymorphic and diverse NK cell receptors in primates and of combinatorial diversity as a novel mechanism to increase NK cell receptor repertoire.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Evolution, Molecular*
  • Histocompatibility Antigens / genetics
  • Histocompatibility Antigens / immunology
  • Humans
  • Mice
  • Models, Molecular
  • NK Cell Lectin-Like Receptor Subfamily D / chemistry
  • NK Cell Lectin-Like Receptor Subfamily D / genetics*
  • NK Cell Lectin-Like Receptor Subfamily D / immunology*
  • Phylogeny
  • Polymorphism, Genetic*
  • Protein Structure, Quaternary
  • Strepsirhini / genetics*
  • Strepsirhini / immunology*

Substances

  • Histocompatibility Antigens
  • NK Cell Lectin-Like Receptor Subfamily D