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Voet%20

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Voet & Voet, Biochemistry. Intracellular Pathogens ... Voet & Voet, Biochemistry. Acquired immunity depends on non-specific protein-peptide interactions ... – PowerPoint PPT presentation

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Title: Voet%20


1
Intracellular Pathogens
Extracellular Pathogens
Voet Voet, Biochemistry
2
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
Peptides bind to MHC Class II molecules in a
common polyproline II conformation
Jardetzky et al., PNAS 93 734-738 (1996)
7
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

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
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
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)
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