Abstract
To determine the nucleotide polymorphism of activating killer-cell immunoglobulin-like receptors (aKIR) 3DS1 and 2DS3, we developed a novel direct-sequencing method and analyzed DNA samples of 175 KIR3DS1+ individuals and 72 KIR2DS3+ individuals from the white population. The putative ligand-binding extracellular immunoglobulin (Ig)-like domains of these aKIR receptors are highly conserved, a scenario contrary to inhibitory KIRs that recognize polymorphic human leukocyte antigen (HLA) class I molecules. Null alleles 3DS1*049N and 2DS3*003N that do not express cell-surface receptors were discovered, and they occur commonly in whites (3DS1*049N = 2%; 2DS3*003N = 0.8%). Sequence-specific polymerase chain reaction (PCR) detecting these null alleles is negative with DNA from nonwhite subjects, suggesting that these null alleles are specific to whites and probably originated after the colonization of modern humans in Europe.
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Acknowledgments
This work was supported by start-up funds from the UCLA Department of Pathology and Laboratory Medicine to Dr. Rajalingam and by funding from the National Marrow Donor Program (NMDP) and the Department of the Navy, Office of Naval Research Cooperative Agreement number N00014-99-2-0006 and Grant number N00014-05-1-0859 to the NMDP. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the Office of Naval Research or the NMDP. We thank John Muramoto for providing DNA samples from the UCLA International Cell and DNA Exchange Programs. We thank Damian Goodridge, Conexio Genomics, Western Australia for his help in building and optimizing KIR libraries for the use in Assign software. Experiments performed in this study comply with the current laws in the USA.
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Luo, L., Du, Z., Sharma, S.K. et al. Chain-terminating natural mutations affect the function of activating KIR receptors 3DS1 and 2DS3. Immunogenetics 59, 779–792 (2007). https://doi.org/10.1007/s00251-007-0239-1
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DOI: https://doi.org/10.1007/s00251-007-0239-1