Antigen Processing and Presentation, Self MHC Restriction, Role of Thymus, and Superantigens

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Antigen Processing and Presentation, Self MHC
Restriction, Role of Thymus, and Superantigens
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What Does The B Cell Immunoglobulin (Ig)
Receptor Recognize?

• Proteins (conformational determinants, denatured
  or proteolyzed determinants)
• Nucleic acids
• Polysaccharides
• Some lipids
• Small chemicals (haptens)

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What Does the aß T Cell Receptor (TCR) Recognize?

• Only fragments of proteins (peptides) associated
  with MHC molecules on surface of cells
• Helper T cells (Th) recognize peptide associated
  with MHC class II molecules
• Cytotoxic T cells (Tc) recognize peptide
  associated with MHC class I molecules

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Experimental Basis for Antigen Processing and
Presentation

• Pulse macrophages with a protein antigen short
  time, wash cells, fix immediately, mix with T
  cells and measure proliferation
• NO PROLIFERATION OF T CELLS
• Pulse macrophages with same protein antigen short
  time, wash cells, fix after 4-5 hours, mix with T
  cells and measure proliferation
• PROLIFERATION OF T CELLS

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Antigen Processing and Presentation

• Fragmentation of protein into peptides
• Association of peptide with an MHC molecule
• Transport to cell surface for expression
• Different cellular pathways for association of
  peptide with MHC class I and class II molecules

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Class I MHC Pathway
Peptide is presented by MHC-I to CD8 cytotoxic T
cell
Globular viral protein - intact
Peptide passes with MHC from Golgi body to
surface
Proteasome degrades protein to peptides
rER
Peptide associates with MHC-I complex
Peptide transporter protein moves
peptide into ER
MHC class I alpha and beta proteins are
made on the rER
Peptide with MHC goes to Golgi body
Golgi body
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Class II MHC Pathway
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Points Concerning Antigen Processing and
Presentation

• 1. Location of pathogen
• viruses in cytosol, MHC class I pathway, Tc
  response
  
• extracellular bacteria, MHC class II pathway, Th2
  response, Ab formation
• intracellular bacteria, MHC class II pathway, Th1
  response

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Points Concerning Antigen Processing and
Presentation

1. Peptides derived from both self and non-self
   proteins can associate with MHC class I and class
   II molecules.
2. Chemical nature of MHC groove determines which
   peptides it will bind.

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Self MHC Restriction

• T cells recognize foreign antigen associated with
  self MHC
• No value for individual to have T cells that
  recognize foreign antigen associated with foreign
  MHC
• Self MHC restriction occurs in thymus

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Th Cell Self MHC Restriction
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Tc Cell Self MHC Restriction
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Process of Self MHC Restriction in Thymus

• T cells with TCR recognizing self MHC molecules
  are retained positive selection
• Retained T cells with TCR recognizing self
  peptide associated with self MHC are eliminated
  negative selection
• Self MHC-restricted T cells are released

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Self MHC Restriction in the Thymus
4 low 8 low
4 - 8 low
Sub-capsular region
Productive TCR rearrangement
Non-productive TCR rearrangement
APOPTOSIS
4 8 TCR
Not recognise self MHC
Recognise self MHC
macrophage
4 8 TCR
TCR recognisesself antigens
Cortex
TCR does not recognise self antigens Negative
selection
Cortico-medullary region
4 8 TCR
4 - 8 -
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Self MHC Restriction in the Thymus
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Self MHC Restriction in the Thymus
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Self MHC Restriction in the Thymus
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Superantigens

• Proteins produced by pathogens
• Not processed by antigen presenting cells
• Intact protein binds to variable region of ß
  chain on TCR of T cells and to MHC class II on
  antigen presenting cells (APC)
• Large numbers of activated T cells release
  cytokines having pathological effects

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Conventional Antigen
Superantigen