1. Antigen Processing & Presentation
Hugh B. Fackrell

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

3. Assigned Reading
Chapter: 10 pp
Janis Kuby’s Immunology 3rd Ed

4. 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

5. MHC antigens codominate53

6. Mixed Lymphocyte Reaction38

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

8. Haplotype Restricted Cytotoxicity56

9. “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

10. T Cell Activation

11. MHC I: Biological function44

12. MHC II: Biological function47

13. MHCII: Biologogical function (2)46

14. MHCII: Function 50

15. 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

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

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

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

19. B Cells
Constitutively express MHC-II
activated
then express B7

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

21. 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

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

23. TAP-1 TAP-2

24. Calnexin & MHC-1

25. 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

26. Endogenous Pathway MHC-i

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

28. 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

29. Invariant chain & MHC-II

30. Exogenous Pathway MHC-II

31. Clinical Applications

32. Performance Objectives

33. 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],

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

35. 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.

36. 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

37. 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.

38. Short Answer Questions

39. 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.

40. 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?

41. DONE!!!