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Article: KIR2DL2/2DL3-E35 alleles are functionally stronger than -Q35 alleles

TitleKIR2DL2/2DL3-E35 alleles are functionally stronger than -Q35 alleles
Authors
Issue Date2016
Citation
Scientific Reports, 2016, v. 6, article no. 23689 How to Cite?
AbstractKIR2DL2 and KIR2DL3 segregate as alleles of a single locus in the centromeric motif of the killer cell immunoglobulin-like receptor (KIR) gene family. Although KIR2DL2/L3 polymorphism is known to be associated with many human diseases and is an important factor for donor selection in allogeneic hematopoietic stem cell transplantation, the molecular determinant of functional diversity among various alleles is unclear. In this study we found that KIR2DL2/L3 with glutamic acid at position 35 (E35) are functionally stronger than those with glutamine at the same position (Q 35). Cytotoxicity assay showed that NK cells from HLA-C1 positive donors with KIR2DL2/L3-E 35 could kill more target cells lacking their ligands than NK cells with the weaker-Q 35 alleles, indicating better licensing of KIR2DL2/L3 + NK cells with the stronger alleles. Molecular modeling analysis reveals that the glutamic acid, which is negatively charged, interacts with positively charged histidine located at position 55, thereby stabilizing KIR2DL2/L3 dimer and reducing entropy loss when KIR2DL2/3 binds to HLA-C ligand. The results of this study will be important for future studies of KIR2DL2/L3-associated diseases as well as for donor selection in allogeneic stem cell transplantation.
Persistent Identifierhttp://hdl.handle.net/10722/294514
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorBari, Rafijul-
dc.contributor.authorThapa, Rajoo-
dc.contributor.authorBao, Ju-
dc.contributor.authorLi, Ying-
dc.contributor.authorZheng, Jie-
dc.contributor.authorLeung, Wing-
dc.date.accessioned2020-12-03T08:22:54Z-
dc.date.available2020-12-03T08:22:54Z-
dc.date.issued2016-
dc.identifier.citationScientific Reports, 2016, v. 6, article no. 23689-
dc.identifier.urihttp://hdl.handle.net/10722/294514-
dc.description.abstractKIR2DL2 and KIR2DL3 segregate as alleles of a single locus in the centromeric motif of the killer cell immunoglobulin-like receptor (KIR) gene family. Although KIR2DL2/L3 polymorphism is known to be associated with many human diseases and is an important factor for donor selection in allogeneic hematopoietic stem cell transplantation, the molecular determinant of functional diversity among various alleles is unclear. In this study we found that KIR2DL2/L3 with glutamic acid at position 35 (E35) are functionally stronger than those with glutamine at the same position (Q 35). Cytotoxicity assay showed that NK cells from HLA-C1 positive donors with KIR2DL2/L3-E 35 could kill more target cells lacking their ligands than NK cells with the weaker-Q 35 alleles, indicating better licensing of KIR2DL2/L3 + NK cells with the stronger alleles. Molecular modeling analysis reveals that the glutamic acid, which is negatively charged, interacts with positively charged histidine located at position 55, thereby stabilizing KIR2DL2/L3 dimer and reducing entropy loss when KIR2DL2/3 binds to HLA-C ligand. The results of this study will be important for future studies of KIR2DL2/L3-associated diseases as well as for donor selection in allogeneic stem cell transplantation.-
dc.languageeng-
dc.relation.ispartofScientific Reports-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleKIR2DL2/2DL3-E35 alleles are functionally stronger than -Q35 alleles-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/srep23689-
dc.identifier.pmid27030405-
dc.identifier.pmcidPMC4814820-
dc.identifier.scopuseid_2-s2.0-84962838941-
dc.identifier.volume6-
dc.identifier.spagearticle no. 23689-
dc.identifier.epagearticle no. 23689-
dc.identifier.eissn2045-2322-
dc.identifier.isiWOS:000373072600001-
dc.identifier.issnl2045-2322-

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