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Novel KIR3DL1 alleles and their expression levels on NK cells: Convergent evolution of KIR3DL1 phenotype variation?

  1. Author:
    Thomas, R.
    Yamada, E.
    Alter, G.
    Martin, M. P.
    Bashirova, A. A.
    Norman, P. J.
    Altfeld, M.
    Parham, P.
    Anderson, S. K.
    McVicar, D. W.
    Carrington, M.

  2. Author Address

    Thomas, Rasmi, Yamada, Eriko, Martin, Maureen P.; Anderson, Stephen K.; McVicar, Daniel W.; Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, Sci Applicat Int Frederick, Frederick, MD 21702 USA. [Alter, Galit, Altfeld, Marcus] Massachusetts Gen Hosp, Infect Dis Unit, Partners AIDS Res Ctr, Boston, MA 02129 USA. [Alter, Galit, Altfeld, Marcus] Harvard Univ, Sch Med, Div AIDS, Boston, MA 02129 USA. [Bashirova, Arman A.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21231 USA. [Norman, Paul J.; Parham, Peter] Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA.
    1. Year: 2008
  2. Journal: Journal of Immunology
    1. 180
    2. 10
    3. Pages: 6743-6750
  4. Type of Article: Article
  1. Abstract:

    KIR3DL1 shows extensive polymorphism, and its variation has functional significance in terms of cell-surface expression levels and inhibitory capacity. We characterized nine KIR3DL1 alleles (*022, *028, *029, *033, *035, *051, *052, *053, and *054), four of which were identified for the first time in this study, and compared them to known alleles in phylogenetic analysis. Blood was available from eight individuals with these alleles, and cell-surface expression on NK cells could be determined for six of them using the KIR3DL1-specific Ab DX9. Four of the alleles were expressed at clearly detectable levels, and two others showed exceptionally low levels of expression. Site-directed mutagenesis demonstrated that single amino acid changes can result in either diminished or enhanced DX9 staining compared with the respective related KIR3DL1 allotypes. These results raise the possibility that KIR3DL1 evolution maintains variation in KIR3DL1 cell-surface expression levels, potentially due to the effect of such variation on functional capacity.

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