ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Copresentation of intact and processed MHC alloantigen by recipient dendritic cells enables delivery of linked help to alloreactive CD8 T cells by indirect-pathway CD4 T cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 55 citations in OpenAlex.
- Graft-derived extracellular vesicles transport miRNAs to modulate macrophage polarization after heart transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025Article
- Immune Landscape in Kidney Transplantation.Journal of inflammation research · 2025Review
- Allorecognition Unveiled: Integrating Recent Breakthroughs Into the Current Paradigm.Transplant international : official journal of the European Society for Organ Transplantation · 2024Review
- Disulfiram, an Anti-alcoholic Drug, Targets Macrophages and Attenuates Acute Rejection in Rat Lung Allografts.Transplant international : official journal of the European Society for Organ Transplantation · 2024Article
- Activation and regulation of alloreactive T cell immunity in solid organ transplantation.Nature reviews. Nephrology · 2022Review
- Therapeutically harnessing extracellular vesicles.Nature reviews. Drug discovery · 2022Review
- The number of donor HLA-derived T cell epitopes available for indirect antigen presentation determines the risk for vascular rejection after kidney transplantation.Frontiers in immunology · 2022Article
- Review
- Designing biomaterials for the modulation of allogeneic and autoimmune responses to cellular implants in Type 1 Diabetes.Acta biomaterialia · 2021Review
- Graft-derived extracellular vesicles transported across subcapsular sinus macrophages elicit B cell alloimmunity after transplantation.Science translational medicine · 2021Article
- High Mobility Group Box 1 Contributes to the Acute Rejection of Liver Allografts by Activating Dendritic Cells.Frontiers in immunology · 2021Article
- Dendritic Cells: Versatile Players in Renal Transplantation.Frontiers in immunology · 2021Review
- The Immunological Basis of Liver Allograft Rejection.Frontiers in immunology · 2020Review
- New insights into the development of B cell responses: Implications for solid organ transplantation.Human immunology · 2019Review
- Mechanisms of Immune Tolerance in Liver Transplantation-Crosstalk Between Alloreactive T Cells and Liver Cells With Therapeutic Prospects.Frontiers in immunology · 2019Review
- Extracellular vesicle-mediated MHC cross-dressing in immune homeostasis, transplantation, infectious diseases, and cancer.Seminars in immunopathology · 2018Review
- T cell Allorecognition Pathways in Solid Organ Transplantation.Frontiers in immunology · 2018Review
- Relative Frequencies of Alloantigen-Specific Helper CD4 T Cells and B Cells Determine Mode of Antibody-Mediated Allograft Rejection.Frontiers in immunology · 2018Article
- Modification of host dendritic cells by microchimerism-derived extracellular vesicles generates split tolerance.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Continuous Acquisition of MHC:Peptide Complexes by Recipient Cells Contributes to the Generation of Anti-Graft CD8American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2017Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
In transplantation, direct-pathway CD8 T cells that recognize alloantigen on donor cells require CD4 help for activation and cytolytic function. The ability of indirect-pathway CD4 T cells to provide this help remains unexplained, because a fundamental requirement for epitope linkage is seemingly broken. The simultaneous presentation, by host dendritic cells (DCs), of both intact MHC class I alloantigen and processed alloantigen would deliver linked help, but has not been demonstrated definitively. In this study, we report that following in vitro coculture with BALB/c DCs, small numbers (~1.5%) of C57BL/6 (B6) DCs presented acquired H-2(d) alloantigen both as processed allopeptide and as unprocessed Ag. This represented class I alloantigen provides a conformational epitope for direct-pathway allorecognition, because B6 DCs isolated from cocultures and transferred to naive B6 mice provoked cytotoxic CD8 T cell alloimmunity. Crucially, this response was dependent upon simultaneous presentation of class II-restricted allopeptide, because despite acquiring similar amounts of H-2(d) alloantigen upon coculture, MHC class II-deficient B6 DCs failed to elicit cytotoxic alloimmunity. The relevance of this pathway to solid-organ transplantation was then confirmed by the demonstration that CD8 T cell cytotoxicity was provoked in secondary recipients by transfer of DCs purified from wild-type, but not from MHC class II-deficient, C57BL/6 recipients of BALB/c heart transplants. These experiments demonstrate that representation of conformationally intact MHC alloantigen by recipient APC can induce cytotoxic alloimmunity, but simultaneous copresentation of processed allopeptide is essential, presumably because this facilitates linked recognition by indirect-pathway CD4 Th cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.