- Matthew E Call, PhD
Matthew E Call, PhD
- Head of Laboratory, Structural Biology Division
- The Walter and Eliza Hall Institute of Medical Research
- Department of Medical Biology
- The University of Melbourne
The mechanism by which an antigen triggers an adaptive immune response involves several steps. Potentially antigenic particles must be captured, processed, and presented in recognizable form to T cells with the appropriate concomitant signals. The cells that perform these functions are antigen-presenting cells (APCs). Most nucleated cells express at least some of the major histocompatibility complex (MHC) proteins required to present antigens to T cells, a feature that endows all cells with the potential to become targets of the immune response when damaged or infected. However, only a select subset of hematopoietic lineage cells possesses the specialized machinery required to efficiently activate or "prime" naïve T cells and thereby initiate a new adaptive immune response. These cells are "professional" APCs.
The antigen processing and T cell priming functions of APCs, as well as clinical implications and applications of these cells, are presented in this topic review. The cellular interactions that form the basis of the cellular immune response and an overview of MHC structure and function are presented separately. (See "The adaptive cellular immune response" and "Major histocompatibility complex (MHC) structure and function".)
Professional APCs — There are three professional APCs:
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- Pamer E, Cresswell P. Mechanisms of MHC class I--restricted antigen processing. Annu Rev Immunol 1998; 16:323.
- Craiu A, Akopian T, Goldberg A, Rock KL. Two distinct proteolytic processes in the generation of a major histocompatibility complex class I-presented peptide. Proc Natl Acad Sci U S A 1997; 94:10850.
- Bjorkman PJ, Saper MA, Samraoui B, et al. Structure of the human class I histocompatibility antigen, HLA-A2. Nature 1987; 329:506.
- Villadangos JA, Ploegh HL. Proteolysis in MHC class II antigen presentation: who's in charge? Immunity 2000; 12:233.
- Honey K, Rudensky AY. Lysosomal cysteine proteases regulate antigen presentation. Nat Rev Immunol 2003; 3:472.
- Cresswell P. Invariant chain structure and MHC class II function. Cell 1996; 84:505.
- Riberdy JM, Newcomb JR, Surman MJ, et al. HLA-DR molecules from an antigen-processing mutant cell line are associated with invariant chain peptides. Nature 1992; 360:474.
- Pos W, Sethi DK, Call MJ, et al. Crystal structure of the HLA-DM-HLA-DR1 complex defines mechanisms for rapid peptide selection. Cell 2012; 151:1557.
- Weber DA, Evavold BD, Jensen PE. Enhanced dissociation of HLA-DR-bound peptides in the presence of HLA-DM. Science 1996; 274:618.
- Stern LJ, Brown JH, Jardetzky TS, et al. Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide. Nature 1994; 368:215.
- Inaba K, Turley S, Iyoda T, et al. The formation of immunogenic major histocompatibility complex class II-peptide ligands in lysosomal compartments of dendritic cells is regulated by inflammatory stimuli. J Exp Med 2000; 191:927.
- Mellman I, Steinman RM. Dendritic cells: specialized and regulated antigen processing machines. Cell 2001; 106:255.
- Beutler B. Toll-like receptors: how they work and what they do. Curr Opin Hematol 2002; 9:2.
- Blander JM, Medzhitov R. Toll-dependent selection of microbial antigens for presentation by dendritic cells. Nature 2006; 440:808.
- von Andrian UH, Mempel TR. Homing and cellular traffic in lymph nodes. Nat Rev Immunol 2003; 3:867.
- O'Keeffe M, Mok WH, Radford KJ. Human dendritic cell subsets and function in health and disease. Cell Mol Life Sci 2015; 72:4309.
- Dustin ML. The immunological synapse. Cancer Immunol Res 2014; 2:1023.
- Rock KL. A new foreign policy: MHC class I molecules monitor the outside world. Immunol Today 1996; 17:131.
- Adiko AC, Babdor J, Gutiérrez-Martínez E, et al. Intracellular Transport Routes for MHC I and Their Relevance for Antigen Cross-Presentation. Front Immunol 2015; 6:335.
- Huang AY, Bruce AT, Pardoll DM, Levitsky HI. In vivo cross-priming of MHC class I-restricted antigens requires the TAP transporter. Immunity 1996; 4:349.
- Shen L, Sigal LJ, Boes M, Rock KL. Important role of cathepsin S in generating peptides for TAP-independent MHC class I crosspresentation in vivo. Immunity 2004; 21:155.
- Houde M, Bertholet S, Gagnon E, et al. Phagosomes are competent organelles for antigen cross-presentation. Nature 2003; 425:402.
- Burgdorf S, Schölz C, Kautz A, et al. Spatial and mechanistic separation of cross-presentation and endogenous antigen presentation. Nat Immunol 2008; 9:558.
- Nair-Gupta P, Baccarini A, Tung N, et al. TLR signals induce phagosomal MHC-I delivery from the endosomal recycling compartment to allow cross-presentation. Cell 2014; 158:506.
- Mori L, Lepore M, De Libero G. The Immunology of CD1- and MR1-Restricted T Cells. Annu Rev Immunol 2016; 34:479.
- Van Kaer L, Wu L, Joyce S. Mechanisms and Consequences of Antigen Presentation by CD1. Trends Immunol 2016; 37:738.
- Schiefner A, Wilson IA. Presentation of lipid antigens by CD1 glycoproteins. Curr Pharm Des 2009; 15:3311.
- Jayawardena-Wolf J, Bendelac A. CD1 and lipid antigens: intracellular pathways for antigen presentation. Curr Opin Immunol 2001; 13:109.
- Keller AN, Corbett AJ, Wubben JM, et al. MAIT cells and MR1-antigen recognition. Curr Opin Immunol 2017; 46:66.
- Le Bourhis L, Martin E, Péguillet I, et al. Antimicrobial activity of mucosal-associated invariant T cells. Nat Immunol 2010; 11:701.
- Serriari NE, Eoche M, Lamotte L, et al. Innate mucosal-associated invariant T (MAIT) cells are activated in inflammatory bowel diseases. Clin Exp Immunol 2014; 176:266.
- Delamarre L, Mellman I. Harnessing dendritic cells for immunotherapy. Semin Immunol 2011; 23:2.
- Valenzuela P, Medina A, Rutter WJ, et al. Synthesis and assembly of hepatitis B virus surface antigen particles in yeast. Nature 1982; 298:347.
- Frazer IH. Development and implementation of papillomavirus prophylactic vaccines. J Immunol 2014; 192:4007.
- Harper DM, DeMars LR. HPV vaccines - A review of the first decade. Gynecol Oncol 2017; 146:196.
- Macri C, Dumont C, Johnston AP, Mintern JD. Targeting dendritic cells: a promising strategy to improve vaccine effectiveness. Clin Transl Immunology 2016; 5:e66.
- Professional APCs
- MAJOR FUNCTIONS
- Monitoring the intracellular environment
- - Antigen acquisition
- - Loading of MHC I molecules
- - Regulation
- Monitoring of the extracellular environment
- - Antigen uptake
- - Antigen processing
- - Loading of MHC II molecules
- - Regulation
- T CELL PRIMING BY APCs
- CROSS-PRESENTATION PATHWAYS
- PRESENTATION OF NONPEPTIDE ANTIGENS
- CD1 presentation of lipid antigens
- MR1 presentation of microbial metabolites
- COOPERATION BETWEEN T AND B CELLS
- CLINICAL RELEVANCE
- Diseases of APCs
- APC-based therapies
- - Vaccination
- APC-based cancer immunotherapy
- - Agents that block APC function
- Antigen-presenting cell functions
- Antigen processing and presentation