Antigens Major histocompatibility complex and antigen presentation (Milan Číž) Antigens Antigens • complete (immunogen) - immunogenicity - specificity • incomplete (hapten) - specificity • antigenic determinants (epitopes) Antigens Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings. antigenic determinants haptens complete antigencarrier Antigens Epitope 1 Epitope 3 Epitope 2 Antibody Antigen Antigen characteristics Physical • relative molecular mass • solubility • electric charge Chemical • structure • degradability Biological • species distance • polypeptides - hormones, synthetic antigens • proteins - plasmatic proteins, enzymes, microbial proteins • polysaccharides – bacterial capsules, synthetic polysacch. • glycoproteins - immunoglobulins, MHC, blood antigens • peptidoglycans – bacterial cell walls • nucleoproteins - chromatin, ribosomes • lipoproteins - plasmatic and cell membranes • lipopolysaccharides - endotoxins from G- bacteria cell walls Chemical composition of immunogens Distinguishing of antigens According to the relation to the given organism • exogenous • endogenous • autoantigens According to the mutual relation between two organisms • xenogenic (heterologous) • allogenic (homologous) • isogenic ~ syngenic (inbred strains, monozygotic twins) • autologous Tumor antigens Tumor-specific antigens (TSAs) • created by tumor specific mutations • present only on tumor cells Tumor-associated antigens (TAAs) • present on tumor cells and normal cells • more common • oncofetal antigens • α-fetoprotein (AFP) • carcinoembryonal antigen (CEA) Antigen presentation Antigen presenting cell T-lymphocyte signal transduction Superantigens Fig. 6.25 Immunobiology, 9/e. (© Garland science 2017) Bacterial superantigen Viral superantigen T-lymphocyte T-lymphocyte Antigens vs. superantigens Immune response ANTIGENS SUPERANTIGENS T-lymphocyte TCR Antigen Superantigen Macrophage HLA II 1 of 10.000 1 of 5 ANTIBODY PRODUCTION Cytokines T- and B-lymphocyt proliferation SEPTIC SHOCK Cytokine overproduction TNF production MHC antigens (MHC = Major Histocompatibility Complex) HLA (Human Leukocyte Antigens) • classical MHC I – HLA-A, HLA-B, HLA-C • non-classical MHC I – HLA-E, HLA-F, HLA-G • MHC II – HLA-DR, HLA-DQ, HLA-DP H-2 (mice) B (chickens) MHC I – all nucleated cells MHC II – antigen presenting cells MHC antigeny Figure 3-19 Immunobiology, 6/e. (© Garland science 2005) Tissue Lymphoid tissue Other nucleated cells Non nucleated cells T-lymphocytes B-lymphocytes Macrophages Other APC Thymic epithelial cells Neutrophils Hepatocytes Kidney Brain Erythrocytes MHC antigens MHC I – peptides bound at their ends MHC II – peptides bound along their entire length MHC antigens 8-10 amino acids 13-35 amino acids Figure 3-23, 3-25 Immunobiology, 6/e. (© Garland science 2005) MHC I – peptides bound at their ends MHC II – peptides bound along their entire length MHC antigens MHC antigens Principal functions of MHC: • MHC I – to bind peptide fragments produced in cell • MHC II – to bind peptide fragments ingested by cell • to present bound peptide fragments to T-lymphocytes MHC antigens Fig. 6.2 Immunobiology, 9/e. (© Garland science 2017) Degraded in Bound to Presented to Consequence Cytosol MHC I CD 8 T-lymphocytes Cell death Endocytic vesicles Endocytic vesicles CD4 T-lymphocytes CD4 T-lymphocytes MHC II MHC II Activation of microbicidal mechanisms Activation of B-lymphocytes (Ab production) Cytosolic pathogens Intravesicular pathogens Extracellular pathogens any cell macrophage B-lymphocyte MHC antigens Figure 8-27 Immunobiology, 6/e. (© Garland science 2005) Cytotoxic T-lymphocyte TH1-lymphocyte TH2-lymphocyte killing activation activation Virus-infected cell macrophage Intra- cellular bacteria Ag-specific B-lymphocyte bacterial toxin Apoptotic cell Killed bacteria B lymphoblast Ab peptide + MHC I peptide + MHC II Intracellular vesicular system Fig. 6.1 Immunobiology, 9/e. (© Garland science 2017) nucleus cytosol endoplasmic reticulum endosome lyzosome autophagosome Golgi apparatus secretory vesicle Peptide fragment presentation via MHC I peptide fragments proteasome protein peptide pump (TAP) Golgi apparatus cytosol endoplasmic reticulum Peptide fragment presentation via MHC II phagosome phagolyzosome lyzosome post-Golgi vesicle cytosol Invariant chain Fig. 6.11 Immunobiology, 9/e. (© Garland science 2017) Ii ER cytosol LIP10 CLIP10 Antigen presenting cells (APC) Fig. 9.13 Immunobiology, 9/e. (© Garland science 2017) Dendritic cell Macrophage B-lymphocyte bacterial antigen viral antigen virus bacterium microbial toxin T lymphocytes meet antigen Langerhans cells Dendritic cells • dendritic cells in different stages of activation and migration • fluorescence microscopy: green – MHC II molecules red – lyzosomal protein Fluorescence microscopy Electron microscopy Antigen presenting cells Antigen presenting cells Antigen presenting cells naivní T-lymfocyt aktivovaný T-lymfocyt