The role of FcRn in antigen presentation
Immunoglobulins are unique molecules capable of simultaneously recognizing a diverse array of antigens and themselves being recognized by a broad array of receptors. The abundance specifically of the IgG subclass and the variety of signaling receptors to which it binds render this an important immun...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2014-08-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00408/full |
| _version_ | 1818163628838223872 |
|---|---|
| author | Kristi eBaker Timo eRath Timo eRath Michal ePyzik Richard S. Blumberg |
| author_facet | Kristi eBaker Timo eRath Timo eRath Michal ePyzik Richard S. Blumberg |
| author_sort | Kristi eBaker |
| collection | DOAJ |
| description | Immunoglobulins are unique molecules capable of simultaneously recognizing a diverse array of antigens and themselves being recognized by a broad array of receptors. The abundance specifically of the IgG subclass and the variety of signaling receptors to which it binds render this an important immunomodulatory molecule. In addition to the classical Fcγ receptors (FcγR) which bind IgG at the cell surface, the neonatal Fc receptor (FcRn) is a lifelong resident of the endolysosomal system of most hematopoietic cells where it determines the intracellular fate of both IgG and IgG-containing immune complexes (IgG IC). Crosslinking of FcRn by multivalent IgG IC within antigen presenting cells such as dendritic cells (DC) initiates specific mechanisms which result in trafficking of the antigen-bearing IgG IC into compartments from which the antigen can successfully be processed into peptide epitopes compatible with loading onto both MHC class I and II molecules. In turn, this enables the synchronous activation of both CD4+ and CD8+ T cell responses against the cognate antigen, thereby bridging the gap between the humoral and cellular branches of the adaptive immune response. Critically, FcRn-driven T cell priming is efficient at very low doses of antigen due to the exquisite sensitivity of the IgG-mediated antigen delivery system through which it operates. FcRn-mediated antigen presentation has important consequences in tissue compartments replete with IgG and serves not only to determine homeostatic immune activation at a variety of sites but also to induce inflammatory responses upon exposure to antigens perceived as foreign. Therapeutically targeting the pathway by which FcRn enables T cell activation in response to IgG IC is thus a highly attractive prospect not only for the treatment of diseases that are driven by immune complexes but also for manipulating local immune responses against defined antigens such as those present during infections and cancer. |
| first_indexed | 2024-12-11T16:52:35Z |
| format | Article |
| id | doaj.art-b4840bf7102a427386868ed1a0da302c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T16:52:35Z |
| publishDate | 2014-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b4840bf7102a427386868ed1a0da302c2022-12-22T00:58:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242014-08-01510.3389/fimmu.2014.00408100377The role of FcRn in antigen presentationKristi eBaker0Timo eRath1Timo eRath2Michal ePyzik3Richard S. Blumberg4Brigham and Women's Hospital and Harvard Medical SchoolBrigham and Women's Hospital and Harvard Medical SchoolErlangen University Hospital, Friedrich Alexander University Erlangen-NuerembergBrigham and Women's Hospital and Harvard Medical SchoolBrigham and Women's Hospital and Harvard Medical SchoolImmunoglobulins are unique molecules capable of simultaneously recognizing a diverse array of antigens and themselves being recognized by a broad array of receptors. The abundance specifically of the IgG subclass and the variety of signaling receptors to which it binds render this an important immunomodulatory molecule. In addition to the classical Fcγ receptors (FcγR) which bind IgG at the cell surface, the neonatal Fc receptor (FcRn) is a lifelong resident of the endolysosomal system of most hematopoietic cells where it determines the intracellular fate of both IgG and IgG-containing immune complexes (IgG IC). Crosslinking of FcRn by multivalent IgG IC within antigen presenting cells such as dendritic cells (DC) initiates specific mechanisms which result in trafficking of the antigen-bearing IgG IC into compartments from which the antigen can successfully be processed into peptide epitopes compatible with loading onto both MHC class I and II molecules. In turn, this enables the synchronous activation of both CD4+ and CD8+ T cell responses against the cognate antigen, thereby bridging the gap between the humoral and cellular branches of the adaptive immune response. Critically, FcRn-driven T cell priming is efficient at very low doses of antigen due to the exquisite sensitivity of the IgG-mediated antigen delivery system through which it operates. FcRn-mediated antigen presentation has important consequences in tissue compartments replete with IgG and serves not only to determine homeostatic immune activation at a variety of sites but also to induce inflammatory responses upon exposure to antigens perceived as foreign. Therapeutically targeting the pathway by which FcRn enables T cell activation in response to IgG IC is thus a highly attractive prospect not only for the treatment of diseases that are driven by immune complexes but also for manipulating local immune responses against defined antigens such as those present during infections and cancer.http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00408/fullAntigen PresentationDendritic CellsIgGFcRnimmune complex |
| spellingShingle | Kristi eBaker Timo eRath Timo eRath Michal ePyzik Richard S. Blumberg The role of FcRn in antigen presentation Frontiers in Immunology Antigen Presentation Dendritic Cells IgG FcRn immune complex |
| title | The role of FcRn in antigen presentation |
| title_full | The role of FcRn in antigen presentation |
| title_fullStr | The role of FcRn in antigen presentation |
| title_full_unstemmed | The role of FcRn in antigen presentation |
| title_short | The role of FcRn in antigen presentation |
| title_sort | role of fcrn in antigen presentation |
| topic | Antigen Presentation Dendritic Cells IgG FcRn immune complex |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00408/full |
| work_keys_str_mv | AT kristiebaker theroleoffcrninantigenpresentation AT timoerath theroleoffcrninantigenpresentation AT timoerath theroleoffcrninantigenpresentation AT michalepyzik theroleoffcrninantigenpresentation AT richardsblumberg theroleoffcrninantigenpresentation AT kristiebaker roleoffcrninantigenpresentation AT timoerath roleoffcrninantigenpresentation AT timoerath roleoffcrninantigenpresentation AT michalepyzik roleoffcrninantigenpresentation AT richardsblumberg roleoffcrninantigenpresentation |