Class II MHC/Peptide Complexes on T Cell Antigen-Presenting Cells: Agonistic Antigen Recognition Inhibits Subsequent Antigen Presentation

1998 ◽  
Vol 186 (2) ◽  
pp. 111-120 ◽  
Author(s):  
Mark D. Mannie ◽  
John P. Nardella ◽  
Gregory A. White ◽  
Paula Y. Arnold ◽  
Daniel K. Davidian
Keyword(s):  
T Cell ◽  
Antigen Presentation ◽  
Antigen Presenting Cells ◽  
Class Ii ◽  
Antigen Recognition ◽  
Cell Antigen ◽  
Class Ii Mhc ◽  
Peptide Complexes ◽  
Antigen Presenting

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

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Eytan Breman ◽  
Jurjen M. Ruben ◽  
Kees L. Franken ◽  
Mirjam H. M. Heemskerk ◽  
Dave L. Roelen ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Antigen Presentation ◽  
Antigen Presenting Cells ◽  
Mannose Receptor ◽  
Class Ii ◽  
Hla Class Ii ◽  
Indirect Allorecognition ◽  
Antigen Presenting

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.

scholarly journals Glatiramer acetate immune modulates B-cell antigen presentation in treatment of MS

2020 ◽  
Vol 7 (3) ◽  
pp. e698 ◽  
Author(s):  
Darius Häusler ◽  
Zivar Hajiyeva ◽  
Jan W. Traub ◽  
Scott S. Zamvil ◽  
Patrice H. Lalive ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Antigen Presentation ◽  
Glatiramer Acetate ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Cell Antigen ◽  
Antigen Presenting

ObjectiveWe examined the effect of glatiramer acetate (GA) on B-cell maturation, differentiation, and antigen presentation in MS and experimental autoimmune encephalomyelitis (EAE).MethodsA cross-sectional study of blood samples from 20 GA-treated and 18 untreated patients with MS was performed by flow cytometry; 6 GA-treated patients with MS were analyzed longitudinally. GA-mediated effects on B-cell antigen-presenting function were investigated in EAE, or, alternatively, B cells were treated with GA in vitro using vehicle as a control.ResultsIn MS, GA diminished transitional B-cell and plasmablast frequency, downregulated CD69, CD25, and CD95 expression, and decreased TNF-α production, whereas IL-10 secretion and MHC Class II expression were increased. In EAE, we observed an equivalent dampening of proinflammatory B-cell properties and an enhanced expression of MHC Class II. When used as antigen-presenting cells for activation of naive T cells, GA-treated B cells promoted development of regulatory T cells, whereas proinflammatory T-cell differentiation was diminished.ConclusionsGA immune modulates B-cell function in EAE and MS and efficiently interferes with pathogenic B cell–T cell interaction.

scholarly journals Ubiquitination by March-I prevents MHC class II recycling and promotes MHC class II turnover in antigen-presenting cells

2015 ◽  
Vol 112 (33) ◽  
pp. 10449-10454 ◽  
Author(s):  
Kyung-Jin Cho ◽  
Even Walseng ◽  
Satoshi Ishido ◽  
Paul A. Roche
Keyword(s):  
B Cells ◽  
Antigen Presentation ◽  
Mhc Class Ii ◽  
Antigen Presenting Cells ◽  
Class Ii ◽  
Mhc Ii ◽  
Class Ii Mhc ◽  
Subsequent Degradation ◽  
Antigen Presenting

MHC class II (MHC-II)-dependent antigen presentation by antigen-presenting cells (APCs) is carefully controlled to achieve specificity of immune responses; the regulated assembly and degradation of antigenic peptide–MHC-II complexes (pMHC-II) is one aspect of such control. In this study, we have examined the role of ubiquitination in regulating pMHC-II biosynthesis, endocytosis, recycling, and turnover in APCs. By using APCs obtained from MHC-II ubiquitination mutant mice, we find that whereas ubiquitination does not affect pMHC-II formation in dendritic cells (DCs), it does promote the subsequent degradation of newly synthesized pMHC-II. Acute activation of DCs or B cells terminates expression of the MHC-II E3 ubiquitin ligase March-I and prevents pMHC-II ubiquitination. Most importantly, this change results in very efficient pMHC-II recycling from the surface of DCs and B cells, thereby preventing targeting of internalized pMHC-II to lysosomes for degradation. Biochemical and functional assays confirmed that pMHC-II turnover is suppressed in MHC-II ubiquitin mutant DCs or by acute activation of wild-type DCs. These studies demonstrate that acute APC activation blocks the ubiquitin-dependent turnover of pMHC-II by promoting efficient pMHC-II recycling and preventing lysosomal targeting of internalized pMHC-II, thereby enhancing pMHC-II stability for efficient antigen presentation to CD4 T cells.

scholarly journals Abortive Proliferation of Rare T Cells Induced by Direct or Indirect Antigen Presentation by Rare B Cells In Vivo

1998 ◽  
Vol 187 (10) ◽  
pp. 1611-1621 ◽  
Author(s):  
Sarah E. Townsend ◽  
Christopher C. Goodnow
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Antigen Presentation ◽  
Cell Fate ◽  
T Cell Activation ◽  
Cell Activation ◽  
Antigen Presenting Cells ◽  
Antigen Presenting

Antigen-specific B cells are implicated as antigen-presenting cells in memory and tolerance responses because they capture antigens efficiently and localize to T cell zones after antigen capture. It has not been possible, however, to visualize the effect of specific B cells on specific CD4+ helper T cells under physiological conditions. We demonstrate here that rare T cells are activated in vivo by minute quantities of antigen captured by antigen-specific B cells. Antigen-activated B cells are helped under these conditions, whereas antigen-tolerant B cells are killed. The T cells proliferate and then disappear regardless of whether the B cells are activated or tolerant. We show genetically that T cell activation, proliferation, and disappearance can be mediated either by transfer of antigen from antigen-specific B cells to endogenous antigen-presenting cells or by direct B–T cell interactions. These results identify a novel antigen presentation route, and demonstrate that B cell presentation of antigen has profound effects on T cell fate that could not be predicted from in vitro studies.

A Crucial Role for Antigen Presenting Cells in Donor CD4+CD25+ Regulatory T Cell Mediated Suppression of Experimental Gvhd.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 688-688
Author(s):  
Isao Tawara ◽  
Tomomi Toubai ◽  
Chelsea Malter ◽  
Yaping Sun ◽  
Evelyn Nieves ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Conflicts Of Interest ◽  
Antigen Presenting Cells ◽  
Class Ii ◽  
Indoleamine 2 ◽  
Effector Phase ◽  
Antigen Presenting

Abstract Abstract 688 Several lines of evidence show that donor derived mature CD4+CD25+Foxp3+ regulatory T cells (Tregs) suppress experimental GVHD. The mechanism of GVHD suppression by donor Tregs is, however, not well understood. Recent observations have brought in a renewed focus on the role of professional antigen presenting cells (APCs) in the induction and maintenance of GVHD by alloreactive T cell effectors (Teffs). But the role of APCs in modulating the responses of Tregs after allogeneic BMT is not known. We first tested the requirement of host APCs in Treg mediated regulation of GVHD. We utilized a clinically relevant CD8+ T cell dependent MHC matched but miHA disparate C3H.SW (H-2b) → wild type (wt) or Class II deficient Abb (II-/-) B6 (H-2b) model of GVHD because host APCs and target tissues from the Abb animals do not express class II and as such donor CD4+CD25+ Tregs will not directly interact with the host tissues while alloreactive CD8+ T cells could still respond to miHA allo-antigens presented by the intact class I on host APCs. The recipient Abb (II-/-) and wt B6 animals were lethally irradiated and transplanted with 2 × 105 CD8+ T cells along with or without CD4+CD25+ Tregs at 1:2 ratio from either syngeneic B6 or allogeneic C3H.SW animals. The wt recipients that received Tregs showed significantly better survival compared with the wt animals that did not receive any Tregs (P< 0.01) while the class II-/- animals showed similar GVHD mortality regardless of Treg infusion (P>0.8). To confirm whether the lack of Treg mediated protection was only due to the absence of interaction with host type APCs and also to exclude the possibility of development of Tregs from the infused BM we thymectomized wt B6 animals and then generated [B6 B6] controls and the [Abb B6] chimeras. These chimeric animals were used as recipients in a second BMT and transplanted with CD8+ Teffs and Tregs from allogeneic C3H.SW mice. Tregs reduced GVHD mortality in the [B6 B6] (P<0.01) but not in the [Abb B6] animals (P>0.7). We next evaluated whether host APC expression of allo-antigens alone was sufficient for Treg mediated GVHD protection in the absence of class II expression on target tissues by generating [B6 B6] and [B6 Abb] chimeras and found that Tregs demonstrated equivalent GVHD protection even when the class II allo-antigens were expressed only on the host APCs. Mechanistic studies demonstrated that Tregs significantly inhibited the expansion of CD8+ Teffs on days +10 and 17 after BMT in the spleens of the WT recipients (P<0.05) but not in the class II-/- animals. However, infused Tregs demonstrated reduced expansion in the class II-/- animals only early after BMT (on day +10) but was equivalent at later time-point (days 17 and 29) to the WT recipients. We further determined the mechanisms by which host APCs might contribute to Treg mediated protection. To this end we used IL-10-/-, indoleamine 2, 3 dioxygenase (IDO)-/- deficient animals and generated [IL-10-/- B6] and [IDO-/- B6] animals as recipients. Tregs mitigated GVHD mortality regardless of the ability of the host APCs to express IL-10 or IDO. We next determined whether Tregs suppressed Teffs in their activation phase at the level of their interaction with host APCs or in the effector phase. C3H.SW CD8+ T cells were primed (both in vivo and ex vivo with B6 allo-antigens) and then infused into the [β2mg-/- B6] animals such that pre-activated CD8 Teffs would still be able to initiate GVHD without the need for host APCs for their activation. Infusion of donor Tregs into [β2mg-/- B6] animals that were transplanted with the pre-activated Teffs mitigated GVHD severity demonstrating that Tregs, once activated by host APCs, were capable of suppressing Teff cells in their effector phase. Collectively our data show (a) host APCs are critical (b) expression of allo-antigens on host target tissues is not obligatory (c) host derived IL-10 and IDO are not critical for Treg mediated GVHD protection and (d) Tregs can mitigate GVHD by suppressing alloreactive Teffs in the effector phase even after they have been activated. Disclosures: No relevant conflicts of interest to declare.

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