Antigen Processing Presentation Hugh B Fackrell 11232020 1
Antigen Processing & Presentation Hugh B. Fackrell 11/23/2020 1
Antigen Processing & Presentation Assigned Reading l Content Outline l Performance Objectives l – Key terms – Key Concepts l Short Answer Questions 11/23/2020 2
Assigned Reading Chapter: 10 pp 249 -262 l Janis Kuby’s Immunology 3 rd Ed l 11/23/2020 3
Content Outline l l l Self MHC Restriction of T Cells Role of Antigen Presenting Cells Two Presentation Pathways Cytosolic Pathway: Endogenous Antigens Endocytic Pathway: Exogenous Antigens Clinical Applications 11/23/2020 4
MHC antigens codominate 11/23/2020 5 53
Mixed Lymphocyte Reaction 11/23/2020 6 38
Self MHC Restriction of T Cells CD 4+ & CD 8+ cells l Antigen must be in cleft of MHC l MHC polymorphism l ~500 antigens/cleft l 11/23/2020 7
Haplotype Restricted Cytotoxicity 11/23/2020 8 56
“Antigen Pulse” “Antigen pulsed” macrophages l T helper (CD 4+) cells can only be stimulated by macrophages with the same MHC Class II l Cytotoxic (CD 8+) T cells can only be stimulated by macrophages with the same MHC Class I l 11/23/2020 9
T Cell Activation 11/23/2020 10
MHC I: Biological function 11/23/2020 44 11
MHC II: Biological function 11/23/2020 47 12
MHCII: Biologogical function (2) 11/23/2020 46 13
MHCII: Function 11/23/2020 50 14
Role of Antigen Presenting Cells Immunize with native protein l Boost with native protein l – B cell & T cell response l Boost with denatured antigen – T cell response only l 2 different mechanisms APC for cell mediated & humoral 11/23/2020 15
Antigen Presenting Cells l Professional APC – Dendritic cells – Macrophages – B Cells l Non Professional APC – Fibroblasts – Glial cells – Thymic epithelial cells – Vascular endothelial cells 11/23/2020 16
Dendritic cells Lot MHC-II l co-stimulate l activate T helpers l 11/23/2020 17
Macrophages l Engulf microbe first – digest antigen – bind to MHC-II l co express with B 7 membrane protein 11/23/2020 18
B Cells Constitutively express MHC-II l activated l then express B 7 l 11/23/2020 19
Two Presentation Pathways l Cytosolic– MHC-I – endogenous antigens l Endocytic – MHC-II – exogenous antigens 11/23/2020 20
Cytosolic Pathway: Endogenous Antigens l Ubiquitin & ATP – Bind to peptide l proteasomes – Bind ubiquitin – peptide transport l Assembly of peptides in MHC-I – Rough Endoplasmic reticulum l Export to membrane 11/23/2020 21
TAP proteins l Transports associated with Antigen Processing – TAP-1 TAP-2 l Transfer Peptides from proteosome to RER 11/23/2020 22
TAP-1 TAP-2 11/23/2020 23
Calnexin & MHC-1 11/23/2020 24
Assembly in RER TAP-1 TAP-2 transport into ER l Bind to Calnexin MHC-I l Add peptide to MHC-I l Release calnexin l Transport to Gogli l 11/23/2020 25
Endogenous Pathway MHC-i 11/23/2020 26
Endocytic Pathway: Exogenous Antigens endocytic vesicles l peptide transport l Assembly of peptides in MHC-II l 11/23/2020 27
Endocytic Route From Outside- phagocytosis l From Inside l – Make MHC-II – Bind Invariant chain – CLIP- digests invariant chain l Fuse – MHC-II & clipped I & peptide – peptide displaces clipped I chain 11/23/2020 28
Invariant chain & MHC-II 11/23/2020 29
Exogenous Pathway MHC-II 11/23/2020 30
Clinical Applications 11/23/2020 31
Performance Objectives 11/23/2020 32
Key Terms antigen presenting cells[253], professional antigen presenting cells[253], l nonprofessional antigen presenting cells[253], cytosolic pathway[255], , l endocytic pathway[258], ubiquitin [255], proteosome[255], l 11/23/2020 33
Transportors associated with antigen processing (TAP) [256], l molecular chaperones[257], calnexin[ 257], invariant (Ii) chain [258], l CLIP [259], l 11/23/2020 34
Key Concepts Describe self MHC restriction. l Compare the cytosolic pathway for antigen presentation with the endocytic pathway for antigen presentation l Compare professional with non professional antigen presenting cells. l 11/23/2020 35
Draw a flow diagram comparing cytosolic and endocytic pathways for processing antigens [Fig 10 -4] l Describe peptide generation by proteasomes. l Describe transport of antigenic peptides from the cytosol to the Rough Endoplasmic reticulum l 11/23/2020 36
Draw a concept map for the separate antigen presenting pathways for endogenous and exogenous antigens. l Describe the assembly of MHC-II molecules within the rough endoplasmic reticulum. l Describe the development of a viral vaccine that uses the cytosolic pathway. l 11/23/2020 37
Short Answer Questions 11/23/2020 38
Describe the development of a vaccine that used the endocytic pathway. l Name thee types of professional APCs. l For each type indicate whether it expresses MHC -II molecules and a co-stimulatory signal constitutively or must be activated before doing so. l Describe the role of ubiquitin in the processing of endogenous antigens. l 11/23/2020 39
Describe the role of calnexin in the assembly of MHC-I. l T cells can react only with protein fragments. l – What is this process called? – How does it occur? Which pathway leads to antigen interaction with MHC-I molecules? l Which pathway leads to interaction with MHC-II molecules? l 11/23/2020 40
DONE!!! 11/23/2020 41
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