Lecture 8: T Cell Development

Question 1

Stages of T Cell Development

Answer 1

1. Lymphocytes start as pluripotent stem cells in the bone marrow.
2. Some stem cells develop into mature IgM+ B cells.
3. Other stem cells develop into T cell precursors.
4. T cell precursors migrate to the thymus.
5. Somatic Recombination in the thymus generates a naive T cell with a unique TCR.

Question 2

A naive thymocyte is made of:

Answer 2

Alpha chain locus
- V, J, C

Beta chain locus
- V, D, J, C

Question 3

Allelic Exclusion

Answer 3

• each individual inherits maternal AND paternal α chain genes.
• Recombinase rearranges V and J gene segments to form an alpha chain.
• If the recombination reaction is productive, recombinase is shut off at the other alpha chain locus.
• Prevents individual cells from expressing more than one TCR.
• The same event occurs during BCR rearrangement.

Question 4

T Cell Receptor (TCR)

Answer 4

• is a heterodimer composed of an α and a β chain.
• each contains a variable 9V) and a constant (C) region.
• The V and C regions are similar in structure to the V and C regions of Antibodies. Likewise, the V regions contribute most to antigen recognition.

Question 5

TCR compared with an Ig molecule

Answer 5

• Both are composed of two chains that combine to form variable and constant domains.
• Both have flexible hinge regions.
• In contrast to an antibody, the TCR is directly and permanently anchored in the plasma membrane. Thus, the C-terminus has no effector functions, it is needed for signaling.

Question 6

MHC-Peptide-TCR Complex

Answer 6

1. Antigenic peptide is bound in the peptide binding groove formed by the α1 and α2 domains of the MHC I molecule.
2. Both α and chains of the TCR interact with the peptide.
3. Additional TCR residues interact with the MHC molecule.

Question 7

The TCR interacts with the _______ and the _________

Answer 7

peptide and MHC

Question 8

CD4 and CD8 do not interact with the antigenic peptide.
They interact with:

Answer 8

CD4 and CD8 interact with NON-POLYMORPHIC residues on MHC class II and I.

Question 9

Features of TCR-mediated antigen recognition

Answer 9

1. TCRs recognize peptides presented by MHC molecules.
2. Each clone is specific for a single antigen.
3. Antigen recognition is mediated by specific domains of the TCR.
4. Signalling triggersT lymphocyte activation.

Question 10

Positive selection (Identifying MHC recognition)

Answer 10

First stage in normal T cell development

Question 11

Self-antigens

Answer 11

collection of thymus and non-thymus peptides

Question 12

TCR development in the Thymus

Answer 12

• Thymic epithelial cell presents self antigen on MHC I and MHC II
• Self-antigens are a collection of thymus and non-thymus peptides

Question 13

What dictates the type (ie. CD4 or CD8) of T cell it will be?

Answer 13

TRC-MHC interaction

Question 14

In positive selection, what happens if TCR recognizes MHC II molecule?

Answer 14

The cell loses CD8 expression. Only CD4 molecules are on the surface.

Question 15

In positive selection, what happens if TCR recognizes MHC I?

Answer 15

The cell loses CD4 expression. Only CD8 molecules are on the surface.

Question 16

A double positive naive lymphocyte contains

Answer 16

both CD8 and CD4 on the surface.

Question 17

What happens if the TCR does not recognize any MHC?

Answer 17

Failure of positive selection.

Non-reactive cell is removed from the thymus through apoptosis.

Question 18

Negative Selection (Identifying TCR-MHC Affinity)

Answer 18

Second stage in normal T cell development

Question 19

Auto-reactive, high affinity self recognizing TCR expressing T cell is removed from the thymus through __________.

Answer 19

apoptosis

Question 20

In TCR development in the thymus, Positive selection along with negative selection generates:

Answer 20

Generation of a pool of CD4 and CD8 lymphocytes with low affinity for self peptide-self MHC complexes

Question 21

Positive selection ensures __________
Negative selection ensures __________

Answer 21

Positive selection: ensures MHC restriction
Negative selection: ensures binding affinity

Question 22

CD4 T cells restricted to ____________
CD8 T cells restricted to ____________

Answer 22

CD4 T cells: restricted to MHC II/ peptide
CD8 T cells: restricted to MHC I/ peptide

Question 23

What happens after selection?

Answer 23

Naive CD4 and CD8 T cells migrate to peripheral lymphoid organs to look for antigen on MHC class I or II.