Antigen process and presentation

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Antigen process and presentation

• Jennifer Nyland, PhD
• Office Bldg1, Room B10
• Phone [phone]
• Email jnyland_at_uscmed.sc.edu

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Teaching objectives

• To compare and contrast Ag recognized by TCR and
  BCR
• To describe the pathways involved in processing
  endogenous and exogenous Ag
• To discuss self MHC restriction in Ag
  presentation to T cells
• To describe the major APCs
• To compare and contrast presentation of
  conventional and superAg
• To discuss the role of positive and negative
  selection in the thymus and generation of self
  MHC restricted Ts

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Comparison of TCR and BCRAg recognition

• BCR
• Soluble or cell associated
• Proteins (conformational and sequence
  determinants)
• Polysaccharides
• Nucleic acids
• Some lipids
• Some chemicals (haptens)
• TCR
• Only peptides associated with MHC on surface of
  APCs
• Th recognize in context of MHC class II
• CTL recognize in context of MHC class I

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Ag processing and presentation

• Ag processing
• Ability of APC to breakdown Ag into peptides and
  associate them with MHC
• Ag presentation
• Process of displaying peptide Ag in context of
  MHC to T cell

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Ag processing pathways
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Ag processing pathway- MHC class I
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Ag processing pathway- MHC class II
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Important aspects of Ag processing

• Location of pathogen dictates type of response
• Virus in cytosol ? MHC class I pathway ? CTL
• Extracellular pathogen ? MHC class II pathway ?
  Th2 response ? Ab production
• Intracellular pathogen in cytosol ? MHC class II
  pathway ? Th1 response ? cytokine production
  (activation of infected cell)

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Important aspects of Ag processing

• Peptides from both self and non-self proteins can
  associate with MHC molecules
• Chemical nature of MHC groove determine which
  peptides will bind
• Anchor sites

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Self MHC restriction

• T cells recognize Ag in context of MHC
• MHC molecules are polymorphic
• Can T cells recognize Ag in any MHC?
• NO
• Ts are restricted to recognizing the context of
  self MHC only

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Ag presenting cells (APCs)

• Dendritic cells (DCs)
• Macrophages
• B cells

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APCs dendritic cells

• Found in the skin (Langerhans cells)
• Ingest Ag by pinocytosis
• Pick up Ag in peripheral tissues and migrate to
  peripheral immune tissues (LN and spleen)
• Most effective APC for activation of naïve Ts
• Can present internalized Ag in context of both
  MHC class I and class II (cross presentation)

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APCs - macrophages

• Ingest Ag by phagocytosis
• Not as effective as DCs in activating naïve Ts
• Effective in activating memory Ts

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APCs B cells

• Bind Ag by surface Ig
• Ingest Ag by endocytosis
• Not as effective as DCs in activating naïve Ts
• Effective in activating memory Ts
• Very effective APCs when Ag concentrations are low

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Presentation of superAg

• Superantigens
• Produced by certain pathogens
• Activate Ts polyclonally
• ? cytokine production
• Can have pathological effects
• Not processed by APC
• Presented by APC in association with MHC class II

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Presentation of superAg

• superAg
• Intact protein binds MHC class II and Vß region
  of TCR
• All Ts with that particular Vß in their TCR
  activated
• ? activation of large numbers of Ts and
  subsequent cytokine release and pathology

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Thymic education
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Thymic education

• How are self MHC-restricted Ts generated?
• Why are self-reacting Ts not produced?
• Random VDJ rearrangements in Ts should generate
  some TCRs that can recognize non-self MHC
• Random VDJ rearrangement should generate some
  TCRs that can recognize self Ag
• Thymic education positive and negative selection

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Thymic education

• Role of the thymus- site of Ts maturation
• Ts with TCR recognizing self MHC are retained
  positive selection
• Retained Ts with TCR recognizing self Ag in self
  MHC are eliminated negative selection
• Remaining Ts are self MHC-restricted and will
  recognize foreign Ag
• Released to periphery

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Thymic education
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Thymic education

• Commitment to CD4 or CD8 T depends on MHC class
  that is encountered

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Negative selection in periphery

• Some self reactive Ts may get to the periphery
• Positive and negative selection is not completely
  effective
• Not all self Ag are expressed in thymus
• Mechanisms to eliminate self-reactive Ts in
  periphery
• Tolerance (lecture 17)

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B cell selection

• Does B cell selection occur?
• No need for positive selection
• Bs are not MHC-restricted
• Negative selection does occur in bone marrow
• Not as critical as for Ts