Characterization of KIR + NK cell subsets with a monoclonal antibody selectively recognizing KIR2DL1 and blocking the specific interaction with HLA-C
The phenotypic identification of different NK cell subsets allows more in-depth characterization of KIR repertoire and function, which are of potential interest in KIR and disease association studies. KIR genes are highly polymorphic, but a great homology exists among the various sequences and few m...
| Autores: | , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Universitat Pompeu Fabra |
| Repositorio: | Repositorio Digital de la UPF |
| OAI Identifier: | oai:repositori.upf.edu:10230/54128 |
| Acceso en línea: | http://hdl.handle.net/10230/54128 http://dx.doi.org/10.1111/tan.14640 |
| Access Level: | acceso abierto |
| Palabra clave: | HLA-C KIR/KIR-ligand interaction Killer immunoglobulin-like receptors Monoclonal antibodies Natural killer cells |
| Sumario: | The phenotypic identification of different NK cell subsets allows more in-depth characterization of KIR repertoire and function, which are of potential interest in KIR and disease association studies. KIR genes are highly polymorphic, but a great homology exists among the various sequences and few monoclonal antibodies (mAbs) specifically recognize a single KIR. This is the case of HP-DM1 which was demonstrated by analysis of cell transfectants and epitope mapping to be exclusively KIR2DL1-specific, covering all allotypes identified to date, except for KIR2DL1*022 and *020, and also to react with KIR2DS1*013. Here, we compared in immunofluorescence analyses the staining of HP-DM1 with other available mAbs to precisely identify KIR2DL1+ NK cells in potential donors for αβT/B-depleted haplo-HSCT, with known KIR genotype. HP-DM1 mAb was used in combination with EB6 or 11PB6 (anti-KIR2DL1/S1 and anti-KIR2DL3*005), 143211 (anti-KIR2DL1/S5), and HP-MA4 (anti-KIR2DL1/S1/S3/S5) mAbs, allowing the accurate identification of different KIR+ NK cell subsets. These phenotypic evaluations appeared useful to dissect the expression pattern of various KIR2D in NK cells from KIR2DL3*005+ individuals, particularly if KIR2DS1 is present. HP-DM1 mAb remarkably refined NK cell phenotyping of donors carrying KIR2DS5, either in the centromeric or telomeric region. Functional assays with KIR2DL1+ /S1+ /S5+ NK cells confirmed that only HP-DM1 exclusively reacts with KIR2DL1. Finally, we demonstrated that HP-DM1 mAb blocked KIR2DL1 recognition of C2+ HLA-C. Altogether, the data support that HP-DM1 is a unique reagent valuable for characterizing KIR+ NK cell subsets. |
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