Lymphocyte Activation
David Low
Clinical Scientist
Lymphocyte Activation
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T-cell APC interaction
Co-stimulation
Early T-cell signaling
Downstream events of TCR signaling
B-cell Response
Mechanisms of B-cell activation
T- cell APC interaction
Naïve Lymphocyte Activation
• Signal 1: low
affinity TCR-MHC
plus peptide
interaction
• Signal 2: mediated
by interaction
between CD28 and
B7 (CD80/86)
Important: Once activated, T cells are able to
proliferate in response to a single signal
TCR/CD3 Co-receptor Complex
• Thought to comprise one
submit each of CD3γand δ
and two subunits of CD3ε
• Two disulphide linked ζ
subunits
• All subunits contain ITAMs
which can become
phosphorylated by kinases
which are activated upon TCR
MHC interaction
Early T-cell signaling events
• Protein Tyrosine Phosphorylation
- Requires CD4/8 interaction
- CD4/8 express Lck, a protein tyrosine kinase
(PTK)
- PTKs can phosphorylate ITAMs found within
the TCR complex
- Recruitment of Zap-70 and subsequent
phosphorylation by Lck
Moving on to Downstream Events
TCR Signaling: Ras/MAPK Pathway
TCR Signaling: Phosphotidylinositol pathway
TCR Signaling: Phosphotidylinositol pathway
B Lymphocyte Activation
Activation
B Cell Co-stimulation (1)
B Cell Co-stimulation (2)
Internalisation of BCR
following direct binding to
antigen leading to
presentation in context of
class II MHC molecule