The avidity of cross-reactive virus-specific T cells for their viral and allogeneic epitopes is variable and depends on epitope expression.

Autor: van den Heuvel H; Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: H.van_den_heuvel@lumc.nl., Heutinck KM; Department of Experimental Immunology, Academic Medical Centre, Amsterdam, The Netherlands; Renal Transplant Unit, Department of Internal Medicine, Division of Internal Medicine, Academic Medical Centre, Amsterdam, The Netherlands., van der Meer-Prins EMW; Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands., Franke-van Dijk MEI; Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands., van Miert PPMC; Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands., Zhang X; Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands., Ten Berge IJM; Renal Transplant Unit, Department of Internal Medicine, Division of Internal Medicine, Academic Medical Centre, Amsterdam, The Netherlands., Claas FHJ; Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Jazyk: angličtina
Zdroj: Human immunology [Hum Immunol] 2018 Jan; Vol. 79 (1), pp. 39-50. Date of Electronic Publication: 2017 Oct 31.
DOI: 10.1016/j.humimm.2017.10.019
Abstrakt: 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 γ (IFNγ) 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.
(Copyright © 2017 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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