Novel multiplex PCR-SSP method for centromeric KIR allele discrimination

Jean Benoît Le Luduec, Anupa Kudva, Jeanette E. Boudreau, Katharine C. Hsu

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8 Citas (Scopus)

Resumen

Allelic diversity of the KIR2DL receptors drive differential expression and ligand-binding affinities that impact natural killer cell function and patient outcomes for diverse cancers. We have developed a global intermediate resolution amplification-refractory mutation system (ARMS) PCR-SSP method for distinguishing functionally relevant subgroups of the KIR2DL receptors, as defined by phylogenetic study of the protein sequences. Use of the ARMS design makes the method reliable and usable as a kit, with all reactions utilizing the same conditions. Six reactions define six subgroups of KIR2DL1; four reactions define three subgroups of KIR2DL2; and five reactions define four subgroups of KIR2DL3. Using KIR allele data from a cohort of 426 European-Americans, we identified the most common KIR2DL subtypes and developed the high-throughput PCR-based methodology, which was validated on a separate cohort of 260 healthy donors. Linkage disequilibrium analysis between the different KIR2DL alleles revealed that seven allelic combinations represent more than 95% of the observed population genotypes for KIR2DL1/L2/L3. In summary, our findings enable rapid typing of the most common KIR2DL receptor subtypes, allowing more accurate prediction of co-inheritance and providing a useful tool for the discrimination of observed differences in surface expression and effector function among NK cells exhibiting disparate KIR2DL allotypes.

Idioma originalEnglish
Número de artículo14853
PublicaciónScientific Reports
Volumen8
N.º1
DOI
EstadoPublished - dic. 1 2018

Nota bibliográfica

Funding Information:
This work was supported by funding from NIH U01 AI069197 and P01 CA23766 to K.C.H., the Francois Wallace Monahan Fellowship to J.B.L., and the Cancer Center Core grant (NIH P03 CA008748) to MSKCC. We thank DKMS Life Science Lab for KIR allele sequencing of our cohort.

Publisher Copyright:
© 2018, The Author(s).

ASJC Scopus Subject Areas

  • General

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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