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Antigen Processing & PresentationHugh B. Fackrell

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Antigen Processing & Presentation

Assigned Reading Content Outline Performance Objectives

– Key terms– Key Concepts

Short Answer Questions

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

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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

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MHC antigens codominate

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Mixed Lymphocyte Reaction

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Self MHC Restriction of T Cells

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

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Haplotype Restricted Cytotoxicity

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“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

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T Cell Activation

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MHC I: Biological function

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MHC II: Biological function

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MHCII: Biologogical function (2)

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MHCII: Function

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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

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Antigen Presenting Cells Professional APC

– Dendritic cells– Macrophages– B Cells

Non Professional APC– Fibroblasts– Glial cells– Thymic epithelial cells– Vascular endothelial cells

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

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Macrophages Engulf microbe first

– digest antigen– bind to MHC-II

co express with B7 membrane protein

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B Cells Constitutively express MHC-II activated then express B7

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Two Presentation Pathways

Cytosolic- – MHC-I– endogenous antigens

Endocytic -– MHC-II– exogenous antigens

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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

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TAP proteins Transports associated with Antigen

Processing– TAP-1 TAP-2

Transfer Peptides from proteosome to RER

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TAP-1 TAP-2

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Calnexin & MHC-1

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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

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Endogenous Pathway

MHC-i

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Endocytic Pathway: Exogenous Antigens

endocytic vesicles peptide transport Assembly of peptides in MHC-II

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Endocytic Route From Outside- phagocytosis From Inside

– Make MHC-II– Bind Invariant chain– CLIP- digests invariant chain

Fuse– MHC-II & clipped I & peptide– peptide displaces clipped I chain

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Invariant chain & MHC-II

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Exogenous Pathway

MHC-II

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Clinical Applications

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Performance Objectives

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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],

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Transportors associated with antigen processing (TAP) [256],

molecular chaperones[257], calnexin[ 257], invariant (Ii) chain [258],

CLIP [259],

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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.

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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

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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.

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Short Answer Questions

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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.

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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?

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DONE!!!DONE!!!