title: Novel KIR3DL1 alleles and their expression levels on NK cells: convergent evolution of KIR3DL1 phenotype variation?
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.
authors.affiliation: Cancer and Inflammation Program, Laboratory of Experimental Immunology, National Cancer Institute, Frederick, MD 21702, USA.
authors.forename: Rasmi
authors.initials: R
authors.lastname: Thomas
authors.forename: Eriko
authors.initials: E
authors.lastname: Yamada
authors.forename: Galit
authors.initials: G
authors.lastname: Alter
authors.forename: Maureen P
authors.initials: MP
authors.lastname: Martin
authors.forename: Arman A
authors.initials: AA
authors.lastname: Bashirova
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Norman
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
authors.forename: Peter
authors.initials: P
authors.lastname: Parham
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Anderson
authors.forename: Daniel W
authors.initials: DW
authors.lastname: McVicar
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D019143:Evolution, Molecular; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007694:Killer Cells, Natural / Q000502:physiology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010641:Phenotype; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D054341:Receptors, KIR3DL1 / Q000737:chemistry / Q000235:genetics*
chemical_list: C515083:KIR3DL1 protein, human; D054341:Receptors, KIR3DL1