T cell

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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
Comparison of BCR and TCR diversity

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
The development of T cells

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
Chronology of positive-negative selection

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

Avidity

Differential signaling hypothesis

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


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