The avidity of cross-reactive virus-specific T cells for their viral and allogeneic epitopes is variable and depends on epitope expression
| Autor: | Marry E.I. Franke-van Dijk, Xiaoqian Zhang, Kirstin M. Heutinck, Ineke J. M. ten Berge, Ellen M.W. van der Meer-Prins, Frans H.J. Claas, Heleen van den Heuvel, Paula P.M.C. van Miert |
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| Přispěvatelé: | Other departments, AII - Infectious diseases, Amsterdam institute for Infection and Immunity, Nephrology |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Isoantigens TCR avidity Immunology Receptors Antigen T-Cell Epitopes T-Lymphocyte Gene Expression T-Cell Antigen Receptor Specificity Streptamer Human leukocyte antigen CD8-Positive T-Lymphocytes Cross Reactions Lymphocyte Activation Epitope Interferon-gamma 03 medical and health sciences 0302 clinical medicine Immune system HLA Antigens Virus-specific T cells Humans Immunology and Allergy Avidity TCR cross-reactivity Antigens Viral Cells Cultured Transplantation biology T-cell receptor General Medicine Molecular biology 030104 developmental biology Virus Diseases Allogeneic HLA biology.protein Antibody Immunologic Memory CD8 030215 immunology |
| Zdroj: | Human Immunology, 79(1), 39-50 Human immunology, 79(1), 39-50. Elsevier Inc. |
| ISSN: | 0198-8859 |
| Popis: | Virus-specific T cells can recognize allogeneic HLA (allo-HLA) through cross-reactivity of their T-cell receptor (TCR). In a transplantation setting, such allo-HLA cross-reactivity may contribute to harmful immune responses towards the allograft, provided that the cross-reactive T cells get sufficiently activated upon recognition of the allo-HLA. An important determinant of T-cell activation is TCR avidity, which to date, has remained largely unexplored for allo-HLA-cross-reactive virus-specific T cells. For this purpose, cold target inhibition assays were performed using allo-HLA-cross-reactive virus-specific memory CD8(+) T-cell clones as responders, and syngeneic cells loaded with viral peptide and allogeneic cells as hot (radioactively-labeled) and cold (non-radioactively-labeled) targets. CD8 dependency of the T-cell responses was assessed using interferon gamma (IFN gamma) enzyme-linked immunosorbent assay (ELISA) in the presence and absence of CD8-blocking antibodies. At high viral-peptide loading concentrations, T-cell clones consistently demonstrated lower avidity for allogeneic versus viral epitopes, but at suboptimal concentrations the opposite was observed. In line, anti-viral reactivity was CD8 independent at high, but not at suboptimal viral-peptide-loading concentrations. The avidity of allo-HLA-cross-reactive virus-specific memory CD8(+) T cells is therefore highly dependent on epitope expression, and as a consequence, can be both higher and lower for allogeneic versus viral targets under different (patho)physiological conditions |
| Databáze: | OpenAIRE |
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