Voet%20

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Intracellular Pathogens
Extracellular Pathogens
Voet Voet, Biochemistry
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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

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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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Antigen Processing and Presentation to Helper
T-cell
Antigen Internalization e.g., via IgG receptor
Endosome/Lysosome
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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)
Ab - Ag
TCR MHC/peptide

• Surface area 2x750 Å2
• gt 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

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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

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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

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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)