MIMM 214 Lecture Notes - Lecture 19: Interferon Gamma, Caspase, Macrophage
7 Jun 2018
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Lecture 20 – February 17, 2017
Effector CTLs can kill infected cells in the periphery
CD8+ T cells
- CTLs recognize and kill infected/tumor cells via TCR activation
- Effector CTL generation from naïve CD8+ precursors
o Signal 1 – TCR binds peptide presented by APC on MHC class I
o Signal 2 – costimulatory signal transmitted by CD28-B7 interaction between T cell and
APC
o Signal 3 – provided by IL-2, inducing proliferation and differentiation into CTL form
- CD8+ specific considerations:
o CD8+ cells require more costimulation
o IL-2 can be autocrine, or paracrine from a Th1 or Th17 cell
CD8+ T cell Activation
Sequential
- APC becomes further licensed following interactions with a CD4+ T cell
o CD40L – CD40
o Increased cytokines and costimulatory molecules
- Interacts with CD8+ T cell independently
Simultaneous
- APC interacts with both CD4+ and CD8+ T cells at the same time
Sequential
- Key part of licensing is signal aPC receives through CD40 signalling
- IL-2 produced by CD8+ T cells alone induces proliferation
Simultaneous
- CD40 signaling due to interaction with CD40L on CD4+ T cell important here too
- IL-2 secreted by both CD4+ and CD8+ T cell induce proliferation of Cd8+ T cell
in both these situations, these are already activated T cells
Question
- What needs to happen to CD4+ T cells in order for CD8+ T cells to activate?
o Activated via pMHC II
o Expression of CD40L
o Signal 3 → Th1 or Th17
- What needs to happen to DCs to allow them to present antigen to both CD4+ and CD8+
o Present on both MHC I & II
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Effector ctls can kill infected cells in the periphery. Ctls recognize and kill infected/tumor cells via tcr activation. Effector ctl generation from na ve cd8+ precursors: signal 1 tcr binds peptide presented by apc on mhc class i, signal 2 costimulatory signal transmitted by cd28-b7 interaction between t cell and. Apc: signal 3 provided by il-2, inducing proliferation and differentiation into ctl form. Cd8+ specific considerations: cd8+ cells require more costimulation. Il-2 can be autocrine, or paracrine from a th1 or th17 cell. Apc becomes further licensed following interactions with a cd4+ t cell: cd40l cd40. Apc interacts with both cd4+ and cd8+ t cells at the same time. Key part of licensing is signal apc receives through cd40 signalling. Il-2 produced by cd8+ t cells alone induces proliferation. Cd40 signaling due to interaction with cd40l on cd4+ t cell important here too.
