Recognition of a virus-encoded ligand by a natural killer cell activation receptor

Smith, Hamish R.C.; Heusel, Jonathan W.; Mehta, Indira K.; Kim, Sung Jin; Dorner, Brigitte G.; Naidenko, Olga V.; Iizuka, Kinji; Furukawa, Hiroshi; Beckman, Diana L.; Pingel, Jeanette T.; Scalzo, Anthony A.; Fremont, Daved H.; Yokoyama, Wayne M.

doi:10.1073/pnas.092258599

Cited by 686 publications

(672 citation statements)

References 46 publications

(47 reference statements)

Supporting

Mentioning

657

Contrasting

Unclassified

Order By: Relevance

“…Ly49H has been shown to bind the MCMV-m157 gene product on infected target cells. 39,43 Other activating Ly49 have been found to bind normal MHC class I from mouse and other rodent species. For example, Ly49D þ NK cells preferentially lyse H-2D d target cells, especially when the NK cells are also negative for inhibitory receptors of H-2D d such as Ly49G.…”

Section: Discussionmentioning

confidence: 99%

Ly49 cluster sequence analysis in a mouse model of diabetes: an expanded repertoire of activating receptors in the NOD genome

et al. 2008

View full text Add to dashboard Cite

The mouse Ly49 and human killer cell immunoglobulin-like receptors (KIR) gene clusters encode activating and inhibitory class I MHC receptors on natural killer (NK) cells. A direct correlation between the presence of multiple activating KIR and various human autoimmune diseases including diabetes has been shown. Previous studies have implicated NK cell receptors in the development of diabetes in the non-obese diabetic (NOD) inbred mouse strain. To assess the contribution of Ly49 to NOD disease acceleration the Ly49 gene cluster of these mice was sequenced. Remarkably, the NOD Ly49 haplotype encodes the largest haplotype and the most functional activating Ly49 of any known mouse strain. These activating Ly49 include three Ly49p-related and two Ly49h-related genes. The NOD cluster contains large regions highly homologous to both C57BL/6 and 129 haplotypes, suggesting unequal crossing over as a mechanism of Ly49 haplotype evolution. Interestingly, the 129-like region has duplicated in the NOD genome. Thus, the NOD Ly49 cluster is a unique mix of elements seen in previously characterized Ly49 haplotypes resulting in a disproportionately large number of functional activating Ly49 genes. Finally, the functionality of activating Ly49 in NOD mice was confirmed in cytotoxicity assays.

show abstract

Section: Discussionmentioning

confidence: 99%

Ly49 cluster sequence analysis in a mouse model of diabetes: an expanded repertoire of activating receptors in the NOD genome

et al. 2008

View full text Add to dashboard Cite

show abstract

“…In contrast, the identification of Ly49H as an activating receptor for the MCMV m157 gene product proves that Ly49H has a direct role in antiviral immunity mediated by B6 NK cells. 31,32 The lack of a gene coding for this type of receptor in the BALB/c haplotype is surprising. Assuming that MCMV is an endemic pathogen in wild mice as human cytomegalovirus is to humans, and that the absence of a Ly49h-like gene is not a result of inbreeding, then it appears that the NK cell-mediated arm of the innate immune system of the BALB/c mouse does not respond to MCMV infection.…”

Section: Discussionmentioning

confidence: 99%

Complete elucidation of a minimal class I MHC natural killer cell receptor haplotype

Dewar

Ml³

et al. 2005

Genes Immun

View full text Add to dashboard Cite

The BALB/c inbred mouse is widely used in models of infectious disease, transplantation, and cancer. The differences in the immune responses of BALB/c compared to C57BL/6 mice are especially valuable for the identification of immune regulation genes. One striking immune variance between these mice is in the function of natural killer (NK) cells, and there is strong evidence implicating differential expression of Ly49 genes. In this study, the complete BALB/c Ly49 gene cluster has been sequenced and found to contain six functional genes and two pseudogenes. Compared to C57BL/6 mice, there is a 200 kb region absent in the BALB/c cluster including a complete lack of Ly49h-related genes, which explains the increased susceptibility of BALB/c to cytomegalovirus infection. In addition, there is no BALB/c Ly49d allele, explaining the inability of BALB/c NK cells to kill certain tumor cells. The Ly49 region has now been sequenced in three different inbred mouse strains, and comparisons indicate that the evolution of each haplotype is not straightforward and has involved large-scale deletions/ insertions, gene recombination, and unequal crossing over between divergent haplotypes. This study confirms that relatively small murine class I MHC receptor haplotypes exist, analogous to observations made of human killer cell Ig-like receptor gene haplotypes.

show abstract

“…8). This model provides an explanation for the skewed repertoire in adaptive NK cells seen in HCMV + individuals towards inhibitory KIR that recognize self HLA class I. Activating KIRs could play a similar role to NKG2C and recognize unknown HCMV‐induced ligands, similarly to Ly49H/m157 in mouse 129, 130…”

Section: Kir Gene Expressionmentioning

confidence: 95%

Deciphering the killer‐cell immunoglobulin‐like receptor system at super‐resolution for natural killer and T‐cell biology

et al. 2016

View full text Add to dashboard Cite

SummaryKiller‐cell immunoglobulin‐like receptors (KIRs) are components of two fundamental biological systems essential for human health and survival. First, they contribute to host immune responses, both innate and adaptive, through their expression by natural killer cells and T cells. Second, KIR play a key role in regulating placentation, and hence reproductive success. Analogous to the diversity of their human leucocyte antigen class I ligands, KIR are extremely polymorphic. In this review, we describe recent developments, fuelled by methodological advances, that are helping to decipher the KIR system in terms of haplotypes, polymorphisms, expression patterns and their ligand interactions. These developments are delivering deeper insight into the relevance of KIR in immune system function, evolution and disease.

show abstract

Recognition of a virus-encoded ligand by a natural killer cell activation receptor

Cited by 686 publications

References 46 publications

Ly49 cluster sequence analysis in a mouse model of diabetes: an expanded repertoire of activating receptors in the NOD genome

Ly49 cluster sequence analysis in a mouse model of diabetes: an expanded repertoire of activating receptors in the NOD genome

Complete elucidation of a minimal class I MHC natural killer cell receptor haplotype

Deciphering the killer‐cell immunoglobulin‐like receptor system at super‐resolution for natural killer and T‐cell biology

Contact Info

Product

Resources

About