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.
https://www.hal.inserm.fr/inserm-03291380 Contributor : Christelle RETIEREConnect in order to contact the contributor Submitted on : Monday, July 19, 2021 - 5:09:40 PM Last modification on : Wednesday, April 27, 2022 - 3:50:03 AM Long-term archiving on: : Wednesday, October 20, 2021 - 7:22:11 PM
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Katia Gagne, Catherine Willem, Nolwenn Legrand, Zakia Djaoud, Gaëlle David, et al.. Both the nature of KIR3DL1 alleles and the KIR3DL1/S1 allele combination affect the KIR3DL1 NK-cell repertoire in the French population. European Journal of Immunology, Wiley-VCH Verlag, 2013, 43 (4), pp.1085 - 1098. ⟨10.1002/eji.201243007⟩. ⟨inserm-03291380⟩