T cell
From IKE
Contents |
Basics
- Part of the immune system
- See processed antigens bound to an MHC molecule through their surface antigen receptor knows as the TCR
- Formed by two disulfide-linked chains pared as αβ (most mature cells) or γδ (<10% of mature cells)
T Cell Receptor
- aka TCR
- Expressed on the T cell surface
- Each TCR recognizes 1 peptide-MHC molecule complex on the surface of an APC
- Similar domain structure as BCRs
- non-covalently associated to the CD3 γ, δ, ε, and ζ chains (1:1:2:2), which is responsible for signalling
- TCRs cannot see antigens as they are put into the system (as compared to BCRs, which can)
- Antigens have to be broken down into peptides and presented by antigen presenting cells before they can be attached and recognized by T cells
- TCRs only have one antigen binding site, instead of two like with immunoglobulins
Signaling
- CD4 and CD8 help in signaling through association with a kinase
Receptor diversity
- TCR diversity is comparable to that of BCRs
- diversity concentrated in the third hypervariable regions of the αβ chains
- Same mechanisms for diversity as BCRs
- Somatic hypermutation does not play a significant role in TCR diversity, though it does in BCR diversity
- Also see Janeway figure 7.22
Development
- T cell development is guided by the following principles:
- Must express TCR genes
- Must have MHC restriction (Bind only to self MHC bound to peptides)
- Must have tolerance
- T cell precursors come from the bone marrow
- Development happens in the thymus
- T cells learn MHC restriction in the cortex of the thymus
- To be activated, a T cell needs the TCR complex and CD4/CD8
- The T cell starts by expressing reactivity to both CD4 and CD8 (double positive)
- The TCR is then exposed to a peptide bound to self MHC on an epithelial cell
- If the TCR attaches to a class 1 MHC, then it expresses CD8 (single positive; class I)
- If the TCR attaches to a class 2 MHC, then it expresses CD4 (single positive; class II)
- That's that for T Cells. They are thereafter released into the periphery
Positive and negative selection
- These two fundamental processes happen to all double-positive thymocytes (CD4+ CD8+)
- Basically a weeding process to ensure that the cells are appropriate
Positive selection
- Only those thymocytes expressing TCR capable of recognizing peptides on self MHC are allowed to proceed in the maturation process
- Process results mainly from interaction between thymocytes with cortical epithelial cells
- This is the the acquisition of MHC restriction
- See Janeway figures 7.11, 7.12, 7.13, 7.22, 7.27, 7.30, 7.31
Negative selection
- Thymocytes with a TCR with very high affinity for self peptides presented by self MHC die by apoptosis
- This is the the acquisition of T cell tolerance
Signals
- Two signaling hypotheses exist, avidity and the differential signaling hypothesis
Avidity
- too low/strong will cause negative selection
- Intermediate strength will cause positive selection
Differential signaling hypothesis
- partial signaling: positive selection
- Full 'agonist' signaling: negative selection
T cell subsets
Based on co-receptor expression
- A coreceptor can be thought of like a partner in a dance.
- Either the embrace works or it doesn't
CD4
- Every immune response starts with CD4+ T cell response
- This is why HIV is so lethal -- it kills all CD4+ T cells
CD8
- MHC Class 1?
Functional subsets
What happened to the people of hiroshima?
- They died
- Those that did not die directly from the bomb subsequently lost their bone marrow (and any rapidly-dividing cells)
- MHC restriction is faciliated by epithelial cells, which is radio resistant
- Tolerance is facilitated by dendritic cells, which are radiosensitive
- If you irradiate somebody, then you could "reset" the conception of self and non-self
- This is not a commonly used treatment because it is worse than the cure in many cases
