1. Intracellular Pathogens Extracellular Pathogens
Voet & Voet, Biochemistry

2. Part 1: Antigen Specific
Acquired immunity depends on many specific protein-protein interactions
Part 1: Antigen Specific
Antibody - Antigen
Cytotoxic T-cell receptor - MHC class I protein/peptide complex
Helper T-cell receptor - MHC class II protein/peptide complex

3. Voet & Voet, Biochemistry

4. Acquired immunity depends on non-specific protein-peptide interactions
MHC class II - peptides generated in the endosome/lysosome (antigens of extracellular origin) recognized by helper T cells
MHC class I - peptides generated in the cytoplasm (antigens of intracellular origin) recognized by cytotoxic T cells

5. Antigen Processing and Presentation to Helper T-cell
Antigen Internalization
e.g., via IgG receptor
Endosome/Lysosome

6. Jardetzky et al., PNAS 93: 734-738 (1996)
Peptides bind to MHC Class II molecules in a common polyproline II conformation
Jardetzky et al., PNAS 93: (1996)

7. Antigen Recognition by Antibodies (Ab) and T-cell Receptors (TCR)
Ab - Ag
TCR – MHC/peptide
Surface area ~ 2x750 Å2
> 50% hydrophobic
1-2 H-bonds
Epitope discontinuous in antigen (Ag) sequence
Surface area ~ 2x1000 Å2
Ag peptide contributes only 40% of surface area
Epitope continuous in Ag sequence
Otherwise similar to Ab - Ag recognition

8. Peptide Binding by Major Histocompatibility Complex (MHC) Antigen-presenting Proteins
MHC I
MHC II
Peptides of intracellular origin
Peptides 9-10 residues long
Deep pockets bind peptide sidechains
Deep pockets bind peptide N- and C-termini
Peptides of extracellular origin
Peptides 15 residues or longer
Shallow pockets bind peptide sidechains
Peptide termini free
H-bonds to peptide backbone

9. Part 2: Transport/Immunoregulatory
Acquired immunity depends on many specific protein-peptide interactions
Part 2: Transport/Immunoregulatory
(a few examples)
IgG receptor - IgG
MHC class II protein - CD4
MHC class I protein - CD8
IL-2 - CD25
TNF - TNF receptor

10. Grakoui et al., Science 285: 221-227 (1999)
The efficiency of antigen processing may control the T-cell cytokine profile for a given epitope by the size of its “immunological synapse”
Grakoui et al., Science 285: (1999)