Analysis of the mouse 129-strain Nkrp1-Clr gene cluster reveals conservation of genomic organization and functional receptor-ligand interactions despite significant allelic polymorphism

Peter Chen; Simon Bélanger; Oscar A. Aguilar; Qiang Zhang; Aaron St.-Laurent; M. Munir Ahmad Rahim; Andrew P. Makrigiannis; James R. Carlyle

doi:10.1007/s00251-011-0542-8

Analysis of the mouse 129-strain Nkrp1-Clr gene cluster reveals conservation of genomic organization and functional receptor-ligand interactions despite significant allelic polymorphism

Peter Chen, Simon Bélanger, Oscar A. Aguilar, Qiang Zhang, Aaron St.-Laurent, M. Munir Ahmad Rahim, Andrew P. Makrigiannis, James R. Carlyle

Research output: Contribution to journal › Article › peer-review

26 Citations (Scopus)

Abstract

The Nkrp1 (Klrb) family of NK cell receptors and their genetically linked Clr (Clec2) ligands are conserved between rodents and humans. Nonetheless, certain mouse and rat Nkrp1 genes exhibit significant allelic polymorphism between inbred strains. We previously demonstrated that the Nkrp1-Clr recognition system is genetically and functionally conserved between the B6 and BALB/c strains, with focused sequence divergence evident in certain genes (e.g., Nkrp1 b,c). Here, we extend this finding by mapping the 129-strain Nkrp1-Clr gene cluster, which is structurally conserved yet displays significant sequence divergence relative to the B6 haplotype. In addition, we show that 129-strain NK cells possess comparable Nkrp1 and Clr transcript expression, and characterize several NKR-P1:Clr interactions that are functionally conserved between the B6 and 129 strains, including documented and novel receptor-ligand pairs. Thus, despite significant allelic polymorphism observed in the Nkrp1-Clr region, the overall genetic organization and functional repertoire appear to be conserved among mouse strains, in contrast to the striking variation observed in the corresponding Ly49 region. These data extend our knowledge of the complex genetically linked Nkrp1-Clr NK recognition system in mice.

Original language	English
Pages (from-to)	627-640
Number of pages	14
Journal	Immunogenetics
Volume	63
Issue number	10
DOIs	https://doi.org/10.1007/s00251-011-0542-8
Publication status	Published - Oct 2011
Externally published	Yes

Bibliographical note

Funding Information:
Acknowledgments We thank Stephen Anderson for assistance with analyzing BAC clones, Lise Kveberg and John Vaage for providing BALB-strain Clr expression constructs, and Colin Brooks for providing a B6 Clrx cDNA vector. This work was supported by an operating grant from the Canadian Institutes of Health Research (CIHR MOP 86630; to A.P.M. & J.R.C), and an early researcher award from the Ontario Ministry of Research and Innovation (to J.R. C). P.C. was supported by an Ontario Graduate Scholarship. S.B. is supported by a Fonds de la recherche en santé Québec scholarship. A. P.M. is the Canada research chair in Innate Pathogen Resistance. J.R.C. holds a CIHR new investigator award and an investigator in the pathogenesis of infectious disease award from the Burroughs Wellcome Fund, USA. The authors have no conflicting financial interests.

ASJC Scopus Subject Areas

Immunology
Genetics

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

Access to Document

10.1007/s00251-011-0542-8

Cite this

Chen, P., Bélanger, S., Aguilar, O. A., Zhang, Q., St.-Laurent, A., Rahim, M. M. A., Makrigiannis, A. P., & Carlyle, J. R. (2011). Analysis of the mouse 129-strain Nkrp1-Clr gene cluster reveals conservation of genomic organization and functional receptor-ligand interactions despite significant allelic polymorphism. Immunogenetics, 63(10), 627-640. https://doi.org/10.1007/s00251-011-0542-8

Analysis of the mouse 129-strain Nkrp1-Clr gene cluster reveals conservation of genomic organization and functional receptor-ligand interactions despite significant allelic polymorphism. / Chen, Peter; Bélanger, Simon; Aguilar, Oscar A. et al.
In: Immunogenetics, Vol. 63, No. 10, 10.2011, p. 627-640.

Research output: Contribution to journal › Article › peer-review

Chen, P, Bélanger, S, Aguilar, OA, Zhang, Q, St.-Laurent, A, Rahim, MMA, Makrigiannis, AP & Carlyle, JR 2011, 'Analysis of the mouse 129-strain Nkrp1-Clr gene cluster reveals conservation of genomic organization and functional receptor-ligand interactions despite significant allelic polymorphism', Immunogenetics, vol. 63, no. 10, pp. 627-640. https://doi.org/10.1007/s00251-011-0542-8

@article{57c2e5b1bbdd41b9a6b97ad4f29bcb37,

title = "Analysis of the mouse 129-strain Nkrp1-Clr gene cluster reveals conservation of genomic organization and functional receptor-ligand interactions despite significant allelic polymorphism",

abstract = "The Nkrp1 (Klrb) family of NK cell receptors and their genetically linked Clr (Clec2) ligands are conserved between rodents and humans. Nonetheless, certain mouse and rat Nkrp1 genes exhibit significant allelic polymorphism between inbred strains. We previously demonstrated that the Nkrp1-Clr recognition system is genetically and functionally conserved between the B6 and BALB/c strains, with focused sequence divergence evident in certain genes (e.g., Nkrp1 b,c). Here, we extend this finding by mapping the 129-strain Nkrp1-Clr gene cluster, which is structurally conserved yet displays significant sequence divergence relative to the B6 haplotype. In addition, we show that 129-strain NK cells possess comparable Nkrp1 and Clr transcript expression, and characterize several NKR-P1:Clr interactions that are functionally conserved between the B6 and 129 strains, including documented and novel receptor-ligand pairs. Thus, despite significant allelic polymorphism observed in the Nkrp1-Clr region, the overall genetic organization and functional repertoire appear to be conserved among mouse strains, in contrast to the striking variation observed in the corresponding Ly49 region. These data extend our knowledge of the complex genetically linked Nkrp1-Clr NK recognition system in mice.",

author = "Peter Chen and Simon B{\'e}langer and Aguilar, {Oscar A.} and Qiang Zhang and Aaron St.-Laurent and Rahim, {M. Munir Ahmad} and Makrigiannis, {Andrew P.} and Carlyle, {James R.}",

note = "Funding Information: Acknowledgments We thank Stephen Anderson for assistance with analyzing BAC clones, Lise Kveberg and John Vaage for providing BALB-strain Clr expression constructs, and Colin Brooks for providing a B6 Clrx cDNA vector. This work was supported by an operating grant from the Canadian Institutes of Health Research (CIHR MOP 86630; to A.P.M. & J.R.C), and an early researcher award from the Ontario Ministry of Research and Innovation (to J.R. C). P.C. was supported by an Ontario Graduate Scholarship. S.B. is supported by a Fonds de la recherche en sant{\'e} Qu{\'e}bec scholarship. A. P.M. is the Canada research chair in Innate Pathogen Resistance. J.R.C. holds a CIHR new investigator award and an investigator in the pathogenesis of infectious disease award from the Burroughs Wellcome Fund, USA. The authors have no conflicting financial interests.",

year = "2011",

month = oct,

doi = "10.1007/s00251-011-0542-8",

language = "English",

volume = "63",

pages = "627--640",

journal = "Immunogenetics",

issn = "0093-7711",

publisher = "Springer Verlag",

number = "10",

}

TY - JOUR

T1 - Analysis of the mouse 129-strain Nkrp1-Clr gene cluster reveals conservation of genomic organization and functional receptor-ligand interactions despite significant allelic polymorphism

AU - Chen, Peter

AU - Bélanger, Simon

AU - Aguilar, Oscar A.

AU - Zhang, Qiang

AU - St.-Laurent, Aaron

AU - Rahim, M. Munir Ahmad

AU - Makrigiannis, Andrew P.

AU - Carlyle, James R.

N1 - Funding Information: Acknowledgments We thank Stephen Anderson for assistance with analyzing BAC clones, Lise Kveberg and John Vaage for providing BALB-strain Clr expression constructs, and Colin Brooks for providing a B6 Clrx cDNA vector. This work was supported by an operating grant from the Canadian Institutes of Health Research (CIHR MOP 86630; to A.P.M. & J.R.C), and an early researcher award from the Ontario Ministry of Research and Innovation (to J.R. C). P.C. was supported by an Ontario Graduate Scholarship. S.B. is supported by a Fonds de la recherche en santé Québec scholarship. A. P.M. is the Canada research chair in Innate Pathogen Resistance. J.R.C. holds a CIHR new investigator award and an investigator in the pathogenesis of infectious disease award from the Burroughs Wellcome Fund, USA. The authors have no conflicting financial interests.

PY - 2011/10

Y1 - 2011/10

N2 - The Nkrp1 (Klrb) family of NK cell receptors and their genetically linked Clr (Clec2) ligands are conserved between rodents and humans. Nonetheless, certain mouse and rat Nkrp1 genes exhibit significant allelic polymorphism between inbred strains. We previously demonstrated that the Nkrp1-Clr recognition system is genetically and functionally conserved between the B6 and BALB/c strains, with focused sequence divergence evident in certain genes (e.g., Nkrp1 b,c). Here, we extend this finding by mapping the 129-strain Nkrp1-Clr gene cluster, which is structurally conserved yet displays significant sequence divergence relative to the B6 haplotype. In addition, we show that 129-strain NK cells possess comparable Nkrp1 and Clr transcript expression, and characterize several NKR-P1:Clr interactions that are functionally conserved between the B6 and 129 strains, including documented and novel receptor-ligand pairs. Thus, despite significant allelic polymorphism observed in the Nkrp1-Clr region, the overall genetic organization and functional repertoire appear to be conserved among mouse strains, in contrast to the striking variation observed in the corresponding Ly49 region. These data extend our knowledge of the complex genetically linked Nkrp1-Clr NK recognition system in mice.

AB - The Nkrp1 (Klrb) family of NK cell receptors and their genetically linked Clr (Clec2) ligands are conserved between rodents and humans. Nonetheless, certain mouse and rat Nkrp1 genes exhibit significant allelic polymorphism between inbred strains. We previously demonstrated that the Nkrp1-Clr recognition system is genetically and functionally conserved between the B6 and BALB/c strains, with focused sequence divergence evident in certain genes (e.g., Nkrp1 b,c). Here, we extend this finding by mapping the 129-strain Nkrp1-Clr gene cluster, which is structurally conserved yet displays significant sequence divergence relative to the B6 haplotype. In addition, we show that 129-strain NK cells possess comparable Nkrp1 and Clr transcript expression, and characterize several NKR-P1:Clr interactions that are functionally conserved between the B6 and 129 strains, including documented and novel receptor-ligand pairs. Thus, despite significant allelic polymorphism observed in the Nkrp1-Clr region, the overall genetic organization and functional repertoire appear to be conserved among mouse strains, in contrast to the striking variation observed in the corresponding Ly49 region. These data extend our knowledge of the complex genetically linked Nkrp1-Clr NK recognition system in mice.

UR - http://www.scopus.com/inward/record.url?scp=80155136979&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80155136979&partnerID=8YFLogxK

U2 - 10.1007/s00251-011-0542-8

DO - 10.1007/s00251-011-0542-8

M3 - Article

C2 - 21667046

AN - SCOPUS:80155136979

SN - 0093-7711

VL - 63

SP - 627

EP - 640

JO - Immunogenetics

JF - Immunogenetics

IS - 10

ER -

Analysis of the mouse 129-strain Nkrp1-Clr gene cluster reveals conservation of genomic organization and functional receptor-ligand interactions despite significant allelic polymorphism

Abstract

Bibliographical note

ASJC Scopus Subject Areas

PubMed: MeSH publication types

Access to Document

Other files and links

Fingerprint

Cite this