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

Genes & Immunity volume 6, pages 481–492 (2005)Cite this article

Abstract

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.

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Accession codes

Accessions

GenBank/EMBL/DDBJ

Abbreviations

129S6:

129S6/SvEvTac

B6:

C57BL/6

NK:

natural killer

KIR:

killer cell Ig-like receptor

PIP:

percent identity plot

ALAK:

adherent lymphokine-activated killer

RFLP:

restriction fragment length polymorphism

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Acknowledgements

We gratefully acknowledge Vince Forgetta, Jessica Wasserscheid, Kevin McKee, and Xiaolan Zhang for sequencing and bioinformatics support. This project has been funded in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. NO1CO12400. This work was also supported in part by an operating grant from the Canadian Institutes for Health Research. APM is a scholar of the Canadian Institutes for Health Research (New Investigator Award).

Author information

Authors and Affiliations

  1. Basic Research Program, SAIC-Frederick, National Cancer Institute-Frederick, Frederick, MD, USA

    S K Anderson

  2. Department of Human Genetics, McGill University, Montréal, QC, Canada

    K Dewar

  3. McGill University and Genome Québec Innovation Centre, Montréal, QC, Canada

    K Dewar & G Leveque

  4. Laboratory of Molecular Immunology, IRCM, Montréal, QC, Canada

    M-L Goulet & A P Makrigiannis

  5. Department of Medicine, Université de Montréal, Montréal, QC, Canada

    A P Makrigiannis

  6. Department of Medicine, Division of Experimental Medicine, McGill University, Montréal, QC, Canada

    A P Makrigiannis

  7. Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada

    A P Makrigiannis

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  1. S K Anderson
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  2. K Dewar
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  3. M-L Goulet
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Correspondence to A P Makrigiannis.

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Animal care was provided in accordance with the procedures outlined in ‘A Guide for the Care and Use of Laboratory Animals’ (National Institutes of Health Publication No. 86-23, 1985). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

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Anderson, S., Dewar, K., Goulet, ML. et al. Complete elucidation of a minimal class I MHC natural killer cell receptor haplotype. Genes Immun 6, 481–492 (2005). https://doi.org/10.1038/sj.gene.6364232

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