Antigen Processing and Presentation PDF
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King Saud bin Abdulaziz University for Health Sciences
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This document provides a detailed overview of antigen processing and presentation, crucial processes in the immune system. It explains the roles of MHC and HLA molecules, types of antigen presentation (endogenous and exogenous), and different antigen-presenting cells. It's designed for an undergraduate health science course or similar context.
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Antigen Processing and Presentation Click to edit Master subtitle style IMMC Objectives ▪ Compare the structure and expression of MHC class I and II (proteins). ▪ Describe the role MHC in regulating the immune response. ▪ D...
Antigen Processing and Presentation Click to edit Master subtitle style IMMC Objectives ▪ Compare the structure and expression of MHC class I and II (proteins). ▪ Describe the role MHC in regulating the immune response. ▪ Discuss the source and types of antigen processed by class I and II molecules. ▪ List professional antigen presenting cells. ▪ Discuss the role of the T helper cell in both cell- mediated and humoral immunity. Introduction ▪ Antigen Recognition by T and B cells: ▪ B cells recognize free antigens using antibodies. ▪ T cells recognize antigens as peptides presented on cell surfaces by MHC molecules. ▪ Major Histocompatibility Complex (MHC): ▪ Encoded by the MHC locus genes. ▪ Acts as a cell-surface vessel to present antigen fragments. ▪ Essential for T-cell engagement via their receptors. ▪ MHC Importance and Discovery: ▪ Named for its role in tissue transplant acceptance or rejection. ▪ 1980 Nobel Prize awarded for discoveries on MHC's role in organ transplants and immune responses. Introduction ▪ Classes of MHC Molecules: ▪ Class I and II: ▪ MHC class I in human is known as HLA class I and MHC class II is known as HLA class II. ▪ Similar shapes, present antigens to T cells but differ in roles and structure. ▪ MHC Structure, Function, and Expression: ▪ Discussion of MHC class I and II structures, genetic organization, and inheritance. ▪ Regulation of MHC gene expression and its role in immunity. ▪ Antigen Processing and Presentation: ▪ Pathways of antigen degradation, association with MHC molecules. ▪ Presentation of these complexes on cell surfaces for T-cell recognition. ▪ Includes unique pathways like cross-presentation and handling of nonpeptide antigens. Antigens Capturing and Processing ▪ Cells encounter the antigens upon crossing the physical barriers and then capture the antigens to engulf the antigens leading to its appearance in either in the cytosol or in a vesicle. ▪ Once a pathogen is inside a cell it needs to be degraded into protein peptides in a sequence event and associate with an MHC molecule. Antigens Presentation ▪ Once an antigen is degraded it needs to be transported to the surface of the cell and displayed within a cleft of an MHC molecule in order to be recognized by TCR on the T lymphocyte. T Cell APC Antigens Presentation ▪ Once an antigen is degraded it needs to be transported to the surface of the cell and displayed within a cleft of an MHC molecule to be recognized by TCR on the T lymphocyte. ▪ List of Antigen Presenting Cells ▪ Macrophages Antigen Presenting Cells ▪ Dendritic Cells ▪ B cells What is Major Histocompatibility Complex (MHC)? ▪ MHC is a set of cell surface molecules encoded by a large genetic complex with multiple loci. ▪ The MHC loci encode 2 major classes of membrane-bound glycoprotiens: ▪ 1. MHC class I ▪ 2. MHC class II ▪ MHC function: ▪ The major function of MHC is to bind to “processed antigen peptides” displayed on the cell surface to be recognized by specific T lymphocytes to initiate an immune response. MHC Class I & II ▪ MHC Class I Molecules: ▪ Found on all nucleated cells. ▪ Present peptides derived from endogenous proteins. ▪ Interact with CD8+ T cells. ▪ MHC Class II Molecules: ▪ Expressed mainly on professional APCs (dendritic cells, macrophages, B cells). ▪ Present peptides derived from exogenous proteins. ▪ Interact with CD4+ T cells. Structure of MHC Class I & II ▪ MHC class I: Consist of 4 domains ▪ (1, 2, 3 and β2-microglobuline) ▪ Is expressed on all cell types ▪ except unnucleated cells (Red Blood Cells) MHC Class I MHC Class II ▪ And is recognized by CD8+ cytotoxic T cells. ▪ MHC class II: Consist of 4 domains ▪ (1, 2, β1and β2) ▪ Is only expressed on antigen presenting cells ▪ (Dendritic cells, Macrophages, B lymphocytes) ▪ And is recognized by CD4+ helper T cells (Th). Human Leukocyte Antigen (HLA) ▪ The Major Histocompatibility Complex in human is known as the human leukocyte antigen (HLA). MHC class I in human is known as HLA class I and MHC class II is known as HLA class II. ▪ HLA class I and class II are polygenic (several loci encoding products with essentially the same function) ▪ HLA class I: HLA-A, HLA-B and HLA-C ▪ HLA class II: HLA-DR, HLA-DP and HLA-DQ ▪ HLA class I and class II are polymorphic (variability of alleles in the species) ▪ There are > 2000 HLA-A alleles , > 3000 HLA-B alleles and > 2000 HLA-C alleles. For example HLA-A2, HLA-A26 and HLA-B50 Types of Presented Antigens ▪ Endogenous antigens are degraded into peptides within the cytosol by proteasomes and assembled with MHC class I. ▪ For example: viruses and tumours. ▪ Exogenous antigens are internalized and degraded within endocytic compartments and subsequently assembled with MHC class II. ▪ For example: bacteria Endogenous antigens: Processing and Presentation ▪ Process by which cells present internal, cellular proteins to T cells. ▪ Protein Degradation: ▪ Cytosolic proteins tagged for degradation by ubiquitin. ▪ Proteasome (immunoproteasome in immune cells) cleaves proteins into peptide fragments. ▪ Peptide Transport: ▪ Peptides transported from cytosol to Endoplasmic reticulum (ER) by transporters associated with antigen processing (TAP) molecules. ▪ TAP preference for peptides 8-10 amino acids in length. ▪ Then they get loaded into MHC class I and transported to the surface of the cell. Kuby Immunology (8th ed) Endogenous antigens: Processing and Presentation ▪ MHC Class I Loading: ▪ In the ER, peptide fragments bind to newly synthesized MHC Class I molecules. ▪ The peptide-MHC Class I complex is stabilized by the addition of β2- microglobulin. ▪ Transport and Expression on Cell Surface: ▪ Complexes are transported to the Golgi apparatus, then to the cell surface. ▪ Presented antigens are now available for recognition by CD8+ T cells. Exogenous Antigens: Processing and Presentation ▪ Process by which cells present external, non-cellular proteins to T cells. ▪ Antigen Uptake: ▪ Antigens are internalized through phagocytosis or endocytosis. ▪ Encapsulated in vesicles that fuse with lysosomes. ▪ Antigen Processing: ▪ In lysosomes, antigens are degraded into peptide fragments. ▪ Acidic environment and lysosomal enzymes facilitate the breakdown. Exogenous Antigens: Processing and Presentation MHC Class II Loading: MHC Class II molecules synthesized in ER with an invariant chain that blocks the peptide- binding groove. In endosomes, invariant chain is cleaved, leaving Class II-associated invariant chain peptide (CLIP) in the groove. Peptide-MHC Class II Complex Formation: CLIP is removed and peptides bind to the MHC Class II molecules. The stable peptide-MHC Class II complexes are transported to the cell surface. Exogenous Antigens: Processing and Presentation Endosome containing degraded Peptides binds to protein (i.e., MHC class II. MHC peptides) fuses with class II + peptide are endosome displayed on the cell containing MHC surface class II MHC Restriction ▪ Phenomenon where T cells recognize antigenic peptides only when presented in conjunction with MHC molecules. ▪ T Cell Recognition: ▪ T cell receptors (TCRs) are designed to recognize a complex of peptide and MHC molecule, not peptide alone. ▪ Specificity towards MHC-peptide complexes ensures that T cells can effectively monitor cellular processes. ▪ Role in Immune Response: ▪ Ensures that T cells only respond to peptides displayed on self-MHC molecules, crucial for distinguishing self from non-self. ▪ Central to the immune system's ability to target infected or dysfunctional cells without harming normal body cells. Clinical Relevance ▪ Transplantation Compatibility: ▪ MHC molecules are major determinants in organ and tissue transplant compatibility. ▪ Mismatches in MHC can lead to transplant rejection. ▪ Autoimmune Diseases: ▪ Certain MHC genotypes are associated with higher risks for autoimmune diseases like Type 1 diabetes and rheumatoid arthritis. ▪ Infectious Diseases: ▪ MHC diversity influences susceptibility to infections and the outcome of diseases like HIV and malaria. ▪ Cancer Immunotherapy: ▪ Understanding MHC involvement in presenting tumor antigens can enhance the effectiveness of cancer vaccines and adoptive T cell therapies. ▪ Personalized Medicine: ▪ MHC profiling can guide personalized medicine approaches, tailoring treatments based on individual MHC makeup to enhance efficacy and reduce adverse effects. 19 Thank you 20