1. Adaptive immunity antigen recognition Y Y Y Y Y Y Y Y Y invading
viruses or bacteria
macrophage
Humoral
Immunity
(Antibody repsonse)
Cell-Mediated
Immunity (CMI)
antigen recognition
cytotoxic
T lymphocyte
B lymphocyte
signals
signals
helper
T lymphocyte Y Y Y Y Y Y Y Y Y
killing of
infected cells
antibody
production

2. Antigens Proteins only, for T cells
Proteins, some polysaccharides for B cells
virus
antigens
epitope T
cell

3. Antigen processing and presentation
T cells only see Ag when presented by an APC
for TH: APC = macrophage or DC, exogenous Ag, MHC II
for TC: APC = infected cell, endogenous Ag, MHC I
MHC Ag
TCR T
processing
presentation
(bound to MHC)
CD4 or 8

4. Antigen processing and presentation
What kinds of cells are APCs for exogenous antigens?
How do the APCs recognize the antigens?
What are MHC proteins?
How does MHC II recognize an antigen peptide?
How does MHC II get loaded with the antigen peptide?
How does the T cell recognize the presented Ag?
Where does T-cell receptor diversity come from?
What about endogenous Ag and MHC I?

5. What kinds of cells are APCs for exogenous antigens?
Immature DCs in epithelia
Langerhans cells
MHC not expressed
Macrophage-like cells
GALT, SALT, MALT…

6. How do the APCs recognize the antigens?
Pattern receptors:
TLRs
Mannose receptor
etc.
Endocytosis
Pinocytosis

7. How do the APCs recognize the antigens?
Activated by inflammatory cytokines
Migration to lymph nodes
Lose adhesion
Express CCR7
Maturation: express MHC

8. How does MHC II recognize an antigen peptide?
Major histocompatibility complex
Large genetic locus on chromosome 6 (HLA)
Highly polymorphic
3 class I genes, 2 alleles each → 6 different proteins
3 class II α genes, 3 β genes, 2 alleles each → 18 proteins
Immunological “fingerprint”

9. MHC structure
class I
class II

10. MHC structure
a chain – multiple alleles
class I
class II

11. MHC structure
b chain – multiple alleles
class I
class II

12. MHC structure
b2 microglobulin – same for every MHC I
class I
class II

13. MHC structure
Immunoglobulin fold
class I
class II

14. MHC structure CD4 binding site (TH) – same for all MHC II class I
class II

15. MHC structure CD8 binding site (TC) – same for all MHC I class I
class II

16. MHC structure
Peptide-binding region
class I
class II
chime tutorial

17. How does MHC II get loaded with the antigen peptide?
How is MHC class II synthesized and localized?
Given its synthesis pathway, where must it encounter Ag?
What restrictions should there be on the peptides it encounters?

18. How does the T cell recognize the presented Ag?
“Immunological synapse” – clustering of proteins in small area
Antigen-specific T-cell receptor binds Ag + MHC
CD4 binds MHC class II
CD28 binds B7 co-stimulator

19. Where does T-cell receptor diversity come from?
Multiple of TCR subunit genes in genome
Recombination during T-cell development in bone marrow
cleavage by VDJ recombinase (RAG-1 + RAG-2)
ligation

20. Where does T-cell receptor diversity come from?
Combinatorial diversity
Junctional diversity

21. Where does T-cell receptor diversity come from?
Selection during development

22. How does MHC I get loaded with antigen peptide?
MHC I recognizes endogenous Ag: synthesized in the cell
Why would Ag be made in the cell?
Where would we want to recognize Ag peptides?