The role of FcRn in antigen presentation

Frontiers in Immunology

Kristi eBaker¹  Richard S. Blumberg¹  Michal ePyzik¹  Timo eRath² 

[1] Brigham and Women's Hospital and Harvard Medical School;Erlangen University Hospital, Friedrich Alexander University Erlangen-Nueremberg;

关键词: Antigen Presentation;    Dendritic Cells;    IgG;    FcRn;    immune complex;   

DOI  :  10.3389/fimmu.2014.00408

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown