Vesicular

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Vesicular
Cytosolic
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Lecture 8Activation of T Lymphocytes
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Where does T Cell Activation Occur?
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T Cell-APC Interactions
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Initiation of T Cell Responses Requires

• Specific Antigen Recognition
• Stable Adhesion of T cells to APCs
• Transduction of Activation Signals to T cells

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Antigen Recognition and TCR-Mediated Signal
Transduction
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Ligand-Receptor Pairs Involved in T Cell
Activation
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Integrins and Antigen in T Cell Activation
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Ligand-Receptor Pairs Involved in T Cell
Activation
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Two Signal Model of T-Cell Activation
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Activation of Naïve TH Cells (CD4 T Cells)

• For activation of TH Cell by APC.
• TCR - MHCAg interaction not enough!

Signal 1
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Activation of Naïve TH (CD4) Cells Needs Signal 2

• For activation of TH Cell by APC.
• TCR - MHCAg interaction not enough!
• Binding B7-CD28-Signal 2

THCell
APC
Signal 1
Signal 2 Provided by Costimulatory Molecules
B7
CD28
Signal 2
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Role of B7-CD28 Costimulation in T Cell Activation
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Role of IL-2 and IL-2 Receptors in T Cell
Proliferation
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Effect of CD28-Mediated Costimulation on T Cell
Proliferation
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Effect of CD28-Mediated Costimulation

• T-cell Proliferation is driven by a growth
  factor/Cytokine called Interleukin-2.
• Necessary for the synthesis and Secretion of IL-2
• Stabilization of IL-2 mRNA (20-30 fold increase
  in IL-2 synthesis)
• Activate transcription factorsAP-1 and NF-kB
  Increase Transcription of IL-2 mRNA.

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Activation in the Absence of Co-Stimulatory
Signals

• T-Cell Tolerance
• Anergy

APC
TH Cell
CD28
B7
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Costimulatory Differences Among APCs
Naive
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CD8 T Cell Activation
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-Vaccinia Virus Vesicular Stomatitis
-Lymphocytic Virus Choriomeningitis Virus
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CD4 Independent
Example Vaccinia and Lymphocytic
Choriomeningitis Virus Infections In Mice
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CD4 T Cell-Dependent Activation of CD8 T Cells