The functions of natural killer (NK) cells are clearly regulated by major histocompatibility complex (MHC) class I molecules on their cellular targets. In mice, this is due to the action of MHC-specific inhibitory receptors belonging to the Ly49 family of lectin-like molecules. The Ly49 receptors are encoded in the NK gene complex (NKC) that contains clusters of genes for other lectin-like receptors on NK cells and other hematopoietic cells. Interestingly, recent studies have shown that some of these lectin-like receptors, belonging to the Nkrp1 family, can recognize other lectin-like molecules, termed Clr, also encoded in the NKC. These genetically linked loci for receptor-ligand pairs suggest a genetic strategy to preserve this interaction and show several other contrasts with Ly49-MHC interactions. In this review, we discuss these issues and summarize recent developments concerning this non-MHC-dependent regulation of NK cell function.

Original languageEnglish
Pages (from-to)77-89
Number of pages13
JournalCurrent topics in microbiology and immunology
StatePublished - Oct 31 2005


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