A brief Powerpoint presentation on the immunology of acquired ...
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Transcript of A brief Powerpoint presentation on the immunology of acquired ...
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Voet & Voet, Biochemistry
Intracellular Pathogens
Extracellular Pathogens
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Acquired immunity depends on many specific protein-protein interactions
• Antibody - Antigen
• Cytotoxic T-cell receptor - MHC class I protein/peptide complex
• Helper T-cell receptor - MHC class II protein/peptide complex
Part 1: Antigen Specific
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Voet & Voet, Biochemistry
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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
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StructuralBreathing
EndoproteolyticCleavage and
MHCII Binding
ExoproteolyticTrimming
Presentation
N C N C
C
C
C
C
N
NN
C
N
N
1
2
3
Antigen-presenting cell
T cell
Antigen-presenting cell
Antigen Internalizatione.g., via IgG receptor
Endosome/Lysosome
Antigen Processing and Presentation to Helper T-cell
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Peptides bind to MHC Class II molecules in a common polyproline II conformation
Jardetzky et al., PNAS 93: 734-738 (1996)
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Antigen Recognition by Antibodies (Ab) and T-cell Receptors (TCR)
• 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
Ab - Ag TCR – MHC/peptide
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Peptide Binding by Major Histocompatibility Complex (MHC)
Antigen-presenting Proteins
• 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
MHC I MHC II
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• IgG receptor - IgG
• MHC class II protein - CD4
• MHC class I protein - CD8
• IL-2 - CD25
• TNF - TNF receptor
Part 2: Transport/Immunoregulatory(a few examples)
Acquired immunity depends on many specific protein-peptide interactions
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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: 221-227 (1999)