Chapter 8: T-cell Development

Question 1

How do T-cell receptors compare to B-cell antibodies structurally?

Answer 1

Both have variable (binding) regions, and constant regions. TCR composed of a and B chain vs heavy and light chain. Has CD3 accessory proteins for signaling to interior of cell vs ITAMS.
Unique: have CD4/CD8 components to interact w/ MHC molecules

Question 2

How do T-cell receptors compare to B-cell antibodies functionally?

Answer 2

They are not secreted.
They do not undergo class switching or affinity maturation.
They have a single antigen binding site (no avidity).
Lower affinity for antigen than an antibody has.

Question 3

What are the five ‘regions’ of the TCR?

Answer 3

Each a or B-chain has an antigen binding site, a variable region, a constant region, a transmembrane region, and a cytoplasmic tail.

Question 4

What is the difference(s) between åß and y∂ T-cells?

Answer 4

y∂ are most commonly Found in gut mucosa in intraepithelial lymphocytes (IELs). They are not MHC restricted so can recognize whole proteins (not just peptides) by cross linking along multiple receptors. Like the heavy chain in B-cells, the ß and ∂ chain develop first

Question 5

What is the T-cell receptor complex?

Answer 5

It includes the TCR proper, as well as the CD3 ITAMS, and CD4 or CD8.

Question 6

What is the function of CD3 accessory proteins in the complex?

Answer 6

Signaling to the interior of the cell

Question 7

What is the function of CD4+ and CD8+ co-receptors?

Answer 7

Interact with MHC molecules

CD4—>Class 2) (CD8+—> Class 1

Question 8

What are the steps of T-cell maturation in the thymus?

Answer 8

1. Lymphoid progenitor cell migrates to the thymus from bone marrow
2. Notch binds, committing them to T-lineage (Now “Pro-T cells”, “thymocyte” or “DN1”)
3. Express CD2, CD44 adhesion, and IL-2 (CD25) to interact with thymus stromal cells to be stimulated by IL-7 and proliferate (Now “Pre-T cells” or “DN2”)
4. Now B and y genes rearrange (if successful, winner’s ‘light chain’ rearranges) If ß chain wins (Now a DN3), expressed on cell surface w/ invariant pre-Tå and CD3.
5. These cells undergo ß-selection, resulting in proliferation/ differentiation. (Now “pre-T cell”, “DN4” or “Pre-DP”
6. Cells that survive ß-selection undergo alpha chain rearrangement to replace the pre-TCRå. (Now “DP” for having both CD4+ and CD8+)
7. Undergo thymic selection- positive selection for ability to react to self-MHC in thymus and negative selection (cannot react too strongly to/ have high affinity for self-antigens) About 2-5% survive both of these selections.

Question 9

What are the outcomes of positive and negative selection, and why are they important?

Answer 9

1. TCR affinity for self is low (90-96%): they fail to be positively selected and undergo “death by neglect”
2. TCR affinity for self is intermediate (2-5%): just right, positively selected and survive
3. TCR affinity for self is high but not too high (<1%): a small number of these develop into regulatory T-cells
4. TCR affinity for self is very high (2-5%): to avoid cells which would trigger autoimmunity and destruction, these cells are negatively selected and destroyed.

Question 10

What cytokine is important for T-cell developmental process?

Answer 10

Notch binding to receptor commits lymphoid progenitor cells to becoming T-cells, but interacting with IL-7 from thymus stromal cells triggers proliferation

Question 11

Types of T-cells and their function

Answer 11

1. Helper T-cells: activation of macrophages, B-cells and other cells
2. Cytotoxic T-cells: killing infected “target cells” and macrophage activation
3. Regulatory T-cells: maintenance of immunological tolerance. Suppress auto-reactive T-cells
4. Natural Killer T-cells: link between adaptive and innate immune system, can release cytokines AND release cell-killing perforin and granzymes
5. Y∂ T-cells: non-MHC restricted intraepithelial lymphocytes found in gut mucosa. Seem to be able to recognize whole proteins and do not require peptide presentation by MHC