Antigen Processing & Presentation Hugh B. Fackrell

Antigen Processing & Presentation Assigned Reading Content Outline Performance Objectives Key terms Key Concepts Short Answer Questions

Assigned Reading Chapter: 10 pp 249-262 Janis Kuby’s Immunology 3rd Ed

Content Outline Self MHC Restriction of T Cells Role of Antigen Presenting Cells Two Presentation Pathways Cytosolic Pathway: Endogenous Antigens Endocytic Pathway: Exogenous Antigens Clinical Applications

MHC antigens codominate 53

Mixed Lymphocyte Reaction 38

Self MHC Restriction of T Cells CD4+ & CD8+ cells Antigen must be in cleft of MHC MHC polymorphism ~500 antigens/cleft

Haplotype Restricted Cytotoxicity 56

“Antigen Pulse” “Antigen pulsed” macrophages T helper (CD4+) cells can only be stimulated by macrophages with the same MHC Class II Cytotoxic (CD8+) T cells can only be stimulated by macrophages with the same MHC Class I

T Cell Activation

MHC I: Biological function 44

MHC II: Biological function 47

MHCII: Biologogical function (2) 46

MHCII: Function 50

Role of Antigen Presenting Cells Immunize with native protein Boost with native protein B cell & T cell response Boost with denatured antigen T cell response only 2 different mechanisms APC for cell mediated & humoral

Antigen Presenting Cells Professional APC Dendritic cells Macrophages B Cells Non Professional APC Fibroblasts Glial cells Thymic epithelial cells Vascular endothelial cells

Dendritic cells Lot MHC-II co-stimulate activate T helpers

Macrophages Engulf microbe first co express with B7 membrane protein digest antigen bind to MHC-II co express with B7 membrane protein

B Cells Constitutively express MHC-II activated then express B7

Two Presentation Pathways Cytosolic- MHC-I endogenous antigens Endocytic - MHC-II exogenous antigens

Cytosolic Pathway: Endogenous Antigens Ubiquitin & ATP Bind to peptide proteasomes Bind ubiquitin peptide transport Assembly of peptides in MHC-I Rough Endoplasmic reticulum Export to membrane

TAP proteins Transports associated with Antigen Processing TAP-1 TAP-2 Transfer Peptides from proteosome to RER

TAP-1 TAP-2

Calnexin & MHC-1

Assembly in RER TAP-1 TAP-2 transport into ER Bind to Calnexin MHC-I Add peptide to MHC-I Release calnexin Transport to Gogli

Endogenous Pathway MHC-i

Endocytic Pathway: Exogenous Antigens endocytic vesicles peptide transport Assembly of peptides in MHC-II

Endocytic Route From Outside- phagocytosis From Inside Fuse Make MHC-II Bind Invariant chain CLIP- digests invariant chain Fuse MHC-II & clipped I & peptide peptide displaces clipped I chain

Invariant chain & MHC-II

Exogenous Pathway MHC-II

Clinical Applications

Performance Objectives

Key Terms antigen presenting cells[253],professional antigen presenting cells[253], nonprofessional antigen presenting cells[253],cytosolic pathway[255],, endocytic pathway[258], ubiquitin [255], proteosome[255],

Transportors associated with antigen processing (TAP) [256], molecular chaperones[257], calnexin[ 257], invariant (Ii) chain [258], CLIP [259],

Key Concepts Describe self MHC restriction. Compare the cytosolic pathway for antigen presentation with the endocytic pathway for antigen presentation Compare professional with non professional antigen presenting cells.

Draw a flow diagram comparing cytosolic and endocytic pathways for processing antigens [Fig 10-4] Describe peptide generation by proteasomes. Describe transport of antigenic peptides from the cytosol to the Rough Endoplasmic reticulum

Draw a concept map for the separate antigen presenting pathways for endogenous and exogenous antigens. Describe the assembly of MHC-II molecules within the rough endoplasmic reticulum. Describe the development of a viral vaccine that uses the cytosolic pathway.

Short Answer Questions

Describe the development of a vaccine that used the endocytic pathway. Name thee types of professional APCs. For each type indicate whether it expresses MHC-II molecules and a co-stimulatory signal constitutively or must be activated before doing so. Describe the role of ubiquitin in the processing of endogenous antigens.

Describe the role of calnexin in the assembly of MHC-I. T cells can react only with protein fragments. What is this process called? How does it occur? Which pathway leads to antigen interaction with MHC-I molecules? Which pathway leads to interaction with MHC-II molecules?

DONE!!!