2. How do T cells recognize antigens?
Two step process
T cells can only recognize peptide bound to MHC
Antigen Processing
Antigen Presentation
Antigen Presenting Cell (APC)
Professional APC

3. MHC class I communicates with Tc cells
Cell biology reminder
MHC I = Intracellular

4. IR to Extracellular Pathogens
(CD4-MHC II)
Antibodies needed
Pathogen recognition/internalization by professional APCs
a. B cells
b. Macrophages
c. Dendritic cells
Phagolysosome degrades proteins to peptides
Peptides:MHC II complex transported to surface
Professional APC contacts CD4 T cells
CD4 TH cells secrete cytokines to signal B cell maturation

5. Receptor mediated Internalization
MHC class II communicates with TH cells
Phagocytosis
Receptor mediated Internalization
MHC II = Extracellular

6. IR to Intracellular Pathogens
(CD8-MHC I)
Antibodies ineffective
Pathogen replicates in the cell and proteins are degraded in the cytoplasm of the cell
Peptides are transported into ER and bind MHC I and transported to the surface
MHC I expressing cells present to CD8 T cells
CD8 T cells (cytotoxic T cell, CTL) kills host cell

7. Figure 3-11
Cytotoxic cells will kill cells infected by virus or intracellular pathogens
Where does this occur = lymph node
Macrophage secretes inflammatory cytokines - increased microbicidal powers
Lymph node

8. Structures involved in MHC Presentation
TCR
CD4 and CD8
MHC1 and MHCII

9. T cell Co-Receptors Binds MHC II TH TC Binds MHC I
Invariant polypeptides
CD4 - Four extracellular Immunoglobulin like domains - binds to MHC II
CD8 - two chains - alpha and beta, IgL domain with a stalk - binds to MHC I
HIV infects CTL by binding to CD4 receptor and gaining entry to the cell
Binds MHC I

10. Figure 3-13 part 1 of 2 Variable Invariant
MHC1 - membrane bound heavy chain (alpha 1 and alpha 2 form peptide binding pocket)
- Beta2 microglobulin invariant , non-covalent association
MHC2 - two membrane bound chains - each chain has 2 domains - beta1 and alpha1 form binding pocket
Do not confuse the beta2 domain with beta2 microglobulin

11. CD8-MHC I
CD4-MHC II
CD4-2
CD8-3

12. Figure 3-15 Degenerate binding specificity Closed Open
Degenerate binding is different from an Ig molecule
This is the TCR view
Ionic and hydrogen bond
8-10 amino acids
13-25 amino acids
Degenerate binding specificity

13. Figure 3-16

14. Peptide Degradation and Transport
Proteosome=Shredder
Transporter associated with antigen processing
Virus uses the cells ribosomes to make it own protein
In response the cell will breakdown some of the viral proteins

15. Chaperones Calnexin Calreticulin Tapasin
Proteins that aid the correct folding and subunit assembly
MHC I polypeptides are transported into the ER. They are partially folded and assembled - stabilized by calnexin
B2M will replace calnexin

16. Bare lymphocyte syndrome
- TAP deficiency
Bare lymphocyte syndrome - 1% MHC level and don’t do well with viral infections - chronic respiratory infections

17. Figure 3-19
Golgi Transport
Acidic process
Vacuolar Transport

18. Prevention of Peptide:MHC II formation in ER
CLIP - class II-associated invariant-chain peptide
Invariant Chain (li) - Prevent peptide binding in ER
- Deliver to vesicles
HLA-DM - Release of CLIP, peptide loading

19. Figure 3-21 part 2 of 3 TCR binds MHC and peptide CDR3 binds peptide
The CDR3 is the main CDR responsible for recognizing processed antigen
CDR1 of the alpha chain has been shown to interact with the N-terminal of the peptide
CDR1 of the beta chain interacts with the C-terminal
CDR2 is thought to recognize the MHC
CDR3 binds peptide
CDR2 binds MHC
CDR1a binds N-terminal
CDR1b bind C-terminal

20. Cytokines can regulate expression
Interferon induces MHC II expression
In some cell types that do not normally make them

21. T-cell Diversity
- Recombination
- Structure of TCR and associated molecules
- Immunodeficiency diseases
Antigen Processing and Presentation
- Intracellular vs Extracellular
- MHC structure