Uptake of HLA Alloantigens via CD89 and CD206 Does Not Enhance Antigen Presentation by Indirect Allorecognition

In organ transplantation, alloantigens are taken up by antigen presenting cells and presented via the indirect pathway to T-cells which in turn can induce allograft rejection. Monitoring of these T-cells is of major importance; however no reliable assay is available to routinely monitor indirect all...

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Main Authors: Eytan Breman, Jurjen M. Ruben, Kees L. Franken, Mirjam H. M. Heemskerk, Dave L. Roelen, Frans H. Claas, Cees van Kooten
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2016/4215684
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author Eytan Breman
Jurjen M. Ruben
Kees L. Franken
Mirjam H. M. Heemskerk
Dave L. Roelen
Frans H. Claas
Cees van Kooten
author_facet Eytan Breman
Jurjen M. Ruben
Kees L. Franken
Mirjam H. M. Heemskerk
Dave L. Roelen
Frans H. Claas
Cees van Kooten
author_sort Eytan Breman
collection DOAJ
description In organ transplantation, alloantigens are taken up by antigen presenting cells and presented via the indirect pathway to T-cells which in turn can induce allograft rejection. Monitoring of these T-cells is of major importance; however no reliable assay is available to routinely monitor indirect allorecognition. Recently we showed that HLA monomers can be successfully used to monitor indirect allorecognition. Targeting antigens to endocytic receptors on antigen presenting cells may further enhance the presentation of antigens via HLA class II and improve the efficiency of this assay. In the current study we explored targeting of HLA monomers to either CD89 expressing monocytes or mannose receptor expressing dendritic cells. Monomer-antibody complexes were generated using biotin-labeled monomers and avidin labeling of the antibodies. We demonstrate that targeting the complexes to these receptors resulted in a dose-dependent HLA class II mediated presentation to a T-cell clone. The immune-complexes were efficiently taken up and presented to T-cells. However, the level of T-cell reactivity was similar to that when only exogenous antigen was added. We conclude that HLA-A2 monomers targeted for presentation through CD89 on monocytes or mannose receptor on dendritic cells lead to proper antigen presentation but do not enhance indirect allorecognition via HLA-DR.
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institution Kabale University
issn 2314-8861
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spelling doaj-art-7d51bfd1bb4d4304ab38afd41f3d8a152025-08-20T03:35:19ZengWileyJournal of Immunology Research2314-88612314-71562016-01-01201610.1155/2016/42156844215684Uptake of HLA Alloantigens via CD89 and CD206 Does Not Enhance Antigen Presentation by Indirect AllorecognitionEytan Breman0Jurjen M. Ruben1Kees L. Franken2Mirjam H. M. Heemskerk3Dave L. Roelen4Frans H. Claas5Cees van Kooten6Department of Nephrology, Leiden University Medical Center (LUMC), 2333 ZA Leiden, NetherlandsDepartment of Nephrology, Leiden University Medical Center (LUMC), 2333 ZA Leiden, NetherlandsDepartment of Immunohematology and Blood Transfusion, LUMC, 2333 ZA Leiden, NetherlandsDepartment of Hematology, LUMC, 2333 ZA Leiden, NetherlandsDepartment of Immunohematology and Blood Transfusion, LUMC, 2333 ZA Leiden, NetherlandsDepartment of Immunohematology and Blood Transfusion, LUMC, 2333 ZA Leiden, NetherlandsDepartment of Nephrology, Leiden University Medical Center (LUMC), 2333 ZA Leiden, NetherlandsIn organ transplantation, alloantigens are taken up by antigen presenting cells and presented via the indirect pathway to T-cells which in turn can induce allograft rejection. Monitoring of these T-cells is of major importance; however no reliable assay is available to routinely monitor indirect allorecognition. Recently we showed that HLA monomers can be successfully used to monitor indirect allorecognition. Targeting antigens to endocytic receptors on antigen presenting cells may further enhance the presentation of antigens via HLA class II and improve the efficiency of this assay. In the current study we explored targeting of HLA monomers to either CD89 expressing monocytes or mannose receptor expressing dendritic cells. Monomer-antibody complexes were generated using biotin-labeled monomers and avidin labeling of the antibodies. We demonstrate that targeting the complexes to these receptors resulted in a dose-dependent HLA class II mediated presentation to a T-cell clone. The immune-complexes were efficiently taken up and presented to T-cells. However, the level of T-cell reactivity was similar to that when only exogenous antigen was added. We conclude that HLA-A2 monomers targeted for presentation through CD89 on monocytes or mannose receptor on dendritic cells lead to proper antigen presentation but do not enhance indirect allorecognition via HLA-DR.http://dx.doi.org/10.1155/2016/4215684
spellingShingle Eytan Breman
Jurjen M. Ruben
Kees L. Franken
Mirjam H. M. Heemskerk
Dave L. Roelen
Frans H. Claas
Cees van Kooten
Uptake of HLA Alloantigens via CD89 and CD206 Does Not Enhance Antigen Presentation by Indirect Allorecognition
Journal of Immunology Research
title Uptake of HLA Alloantigens via CD89 and CD206 Does Not Enhance Antigen Presentation by Indirect Allorecognition
title_full Uptake of HLA Alloantigens via CD89 and CD206 Does Not Enhance Antigen Presentation by Indirect Allorecognition
title_fullStr Uptake of HLA Alloantigens via CD89 and CD206 Does Not Enhance Antigen Presentation by Indirect Allorecognition
title_full_unstemmed Uptake of HLA Alloantigens via CD89 and CD206 Does Not Enhance Antigen Presentation by Indirect Allorecognition
title_short Uptake of HLA Alloantigens via CD89 and CD206 Does Not Enhance Antigen Presentation by Indirect Allorecognition
title_sort uptake of hla alloantigens via cd89 and cd206 does not enhance antigen presentation by indirect allorecognition
url http://dx.doi.org/10.1155/2016/4215684
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