Characterization of + cell subsets with a monoclonal antibody selectively recognizing and blocking the specific interaction with

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...

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Detalles Bibliográficos
Autores: Meazza, Raffaella|||0000-0003-0242-3157, Falco, Michela|||0000-0002-0317-9830, Canevali, Paolo|||0000-0002-0029-1376, Loiacono, Fabrizio|||0000-0001-9370-8910, Colomar-Carando, Natalia|||0000-0001-9716-181X, Muntasell i Castellví, Aura|||0000-0003-2894-0486, Rea, Anna|||0000-0003-1307-8045, Mingari, Maria Cristina|||0000-0001-6998-5459, Locatelli, Franco|||0000-0002-7976-3654, Moretta, Lorenzo|||0000-0003-4658-1747, López-Botet, Miguel|||0000-0003-4882-065X, Pende, Daniela|||0000-0003-1565-451X
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:281798
Acceso en línea:https://ddd.uab.cat/record/281798
https://dx.doi.org/urn:doi:10.1111/tan.14640
Access Level:acceso abierto
Palabra clave:HLA-C
Killer immunoglobulin-like receptors
KIR/KIR-ligand interaction
Monoclonal antibodies
Natural killer cells
Descripción
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.