title: Both the nature of KIR3DL1 alleles and the KIR3DL1/S1 allele combination affect the KIR3DL1 NK-cell repertoire in the French population.
abstract: NK-cell functions are regulated by many activating and inhibitory receptors including KIR3DL1. Extensive allelic polymorphism and variability in expression can directly alter NK-cell phenotype and functions. Here we investigated the KIR3DL1(+) NK-cell repertoire, taking into account the allelic KIR3DL1/S1 polymorphism, KIR3DL1 phenotype, and function. All 109 studied individuals possessed at least one KIR3DL1 allele, with weak KIR3DL1*054, or null alleles being frequently present. In KIR3DL1(high/null) individuals, we observed a bimodal distribution of KIR3DL1(+) NK cells identified by a different KIR3DL1 expression level and cell frequency regardless of a similar amount of both KIR3DL1 transcripts, HLA background, or KIR2D expression. However, this bimodal distribution can be explained by a functional selection following a hierarchy of KIR3DL1 receptors. The higher expression of KIR3DL1 observed on cord blood NK cells suggests the expression of the functional KIR3DL1*004 receptors. Thus, the low amplification of KIR3DL1(high) , KIR3DL1*004 NK-cell subsets during development may be due to extensive signaling via these two receptors. Albeit in a nonexclusive manner, individual immunological experience may contribute to shaping the KIR3DL1 NK-cell repertoire. Together, this study provides new insight into the mechanisms regulating the KIR3DL1 NK-cell repertoire.
authors: Etablissement Français du Sang and Université de Nantes, EA4271 Immunovirologie et Polymorphisme Génétique, Nantes, France. katia.gagne@efs.sante.fr
authors: Katia
authors: K
authors: Gagne
authors: Catherine
authors: C
authors: Willem
authors: Nolwenn
authors: N
authors: Legrand
authors: Zakia
authors: Z
authors: Djaoud
authors: Gaëlle
authors: G
authors: David
authors: Pauline
authors: P
authors: Rettman
authors: Céline
authors: C
authors: Bressollette-Bodin
authors: David
authors: D
authors: Senitzer
authors: Julie
authors: J
authors: Esbelin
authors: Anne
authors: A
authors: Cesbron-Gautier
authors: Thierry
authors: T
authors: Schneider
authors: Christelle
authors: C
authors: Retière
mesh_terms: D000483:Alleles; D005602:France; D005787:Gene Frequency; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D010641:Phenotype; D054341:Receptors, KIR3DL1 / Q000235:genetics*; D054349:Receptors, KIR3DS1 / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D054341:Receptors, KIR3DL1; D054349:Receptors, KIR3DS1