KIR2DL3 and KIR2DL1 show similar impact on licensing of human NK cells
| Autor: | Malcolm J. W. Sim, Ruhena Sergeant, Eric O. Long, Daniel M. Altmann, Janet Stowell, Rosemary J. Boyton |
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| Přispěvatelé: | Welton Foundation, National Institutes of Health, Wellcome Trust, Imperial College Healthcare NHS Trust- BRC Funding |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
NK cell (NKC) Killer immunoglobulin-like receptor (KIR) Short Communication Immunology Cell Killer immunoglobulin‐like receptor (KIR) NK cells Human leukocyte antigen HLA-C Antigens Biology Lymphocyte Activation Flow cytometry 03 medical and health sciences 0302 clinical medicine Signal strength KIR2DL1 medicine Immunology and Allergy Humans human Receptor Innate immunity medicine.diagnostic_test Degranulation Flow Cytometry Inhibitory receptors Human leukocyte antigen (HLA) Rheostat model Lymphocyte Subsets KIR HLA Killer Cells Natural 030104 developmental biology medicine.anatomical_structure Licensing 1107 Immunology Receptors KIR2DL3 Receptors KIR2DL1 KIR3DL1 030215 immunology |
| Zdroj: | European Journal of Immunology |
| ISSN: | 1521-4141 0014-2980 |
| Popis: | Killer cell immunoglobulin-like receptor/HLA class I (KIR/HLA-I) combinations are associated with disease risk, implicating functional roles for NK cells (NKCs) or KIR(+) T cells. KIR/HLA-I interactions can act through inhibition of NKC activation by target cells and NKC licensing for greater intrinsic responsiveness. We compared licensing conferred by the weaker, HLA-C group 1/KIR2DL3, and the stronger, HLA-C group 2/KIR2DL1, inhibitory combinations. The "rheostat model" predicts weaker licensing by HLA-C1/KIR2DL3 interactions than HLA-C2/KIR2DL1. We analyzed degranulation in NKC subsets expressing single and multiple receptors for HLA-I. NKG2A had the strongest licensing impact, while KIR2DL3, KIR2DL1, and KIR3DL1 were weaker, and not significantly different to each other. Presence of one or two matched HLA-C allotypes did not alter licensing of KIR2DL3(+) and KIR2DL1(+) NKC. Coexpression of activating KIR2DS1 disarmed KIR2DL3(+) and KIR2DL1(+) NKC to a similar extent. KIR3DL1 and NKG2A combined for more enhanced licensing of double-positive NKC than the combination of KIR2DL3 and KIR2DL1. Thus, KIR2DL3 and KIR2DL1 have similar capacity to license NKC, suggesting that inhibitory signal strength and amount of available HLA-C ligands do not correlate with NKC licensing. Altogether, our results show that the basis for disease associations of HLA-C and KIR2DL likely encompasses factors other than licensing. |
| Databáze: | OpenAIRE |
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