T-Cell Development

Question 1

Where do T cell precursors migrate?

Answer 1

To the thymus

Question 2

What generates a naive T cell with a unique TCR?

Answer 2

Somatic recombination in the thymus

Question 3

How is an alpha chain formed?

Answer 3

Recombinase rearranges V and J gene segments to form an alpha chain

Question 4

What happens if the recombination reaction is productive and why?

Answer 4

Recombinase is shut off at the other alpha chain locus to prevent individual cells from expressing more than one TCR

Question 5

What is the structure of a TCR like?

Answer 5

A heterodimer composed of an alpha and beta chain
Each chain contains a V and C region

Question 6

What region on a TCR recognizes antigens?

Answer 6

The V region

Question 7

What are some similarities between TCRs and Ig molecules?

Answer 7

Both are composed of two chains that combine to form variable and constant regions
Both have flexible hinge regions

Question 8

What is the difference between TCRs and Ig molecules?

Answer 8

The TCR is directly and permanently anchored in the plasma membrane and thus the C-terminus has no effector functions and is needed for signaling

Question 9

What do CD4 and CD8 interact with?

Answer 9

Non-polymorphic residues in MCH class 1 and 2, not the antigenic peptide

Question 10

What are the forms of antigens recognized by TCRs?

Answer 10

Peptides displayed by MHC molecules on APCs
Linear epitopes

Question 11

What is the diversity of TCRs?

Answer 11

Each clone has a unique specificity

Question 12

What is antigen recognition mediated by in TCRs?

Answer 12

Variable regions of the alpha and beta chains

Question 13

What are the signaling functions mediated by in TCRs?

Answer 13

Proteins associated with TCR

Question 14

How does TCR develop in the thymus?

Answer 14

Thymic epithelial cells presents self antigen on MCH 1 and 2

Question 15

What are self-antigens?

Answer 15

A collection of thymus and non-thymus peptides

Question 16

What is positive selection?

Answer 16

When the TCR-MHC interaction determines they type of T cell it will be

Question 17

If a TCR recognizes an MHC 2 molecule, what happens?

Answer 17

The cell loses the CD8 expression and becomes a CD4 T cell

Question 18

What happens if the TCR recognizes no MHC?

Answer 18

Failure of positive selection/death by neglect
Non-reactive T cell is removed from the thymus through apoptosis

Question 19

What is negative selection?

Answer 19

When auto-reactive, high affinity self recognizing TCR expressing T cells are removed from the thymus through apoptosis

Question 20

What does positive and negative selection generate?

Answer 20

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

Question 21

What does positive and negative selection ensure?

Answer 21

Positive = ensures MHC restriction
Negative = ensure binding affinity

Question 22

What are CD4 and CD8 T cells restricted to?

Answer 22

CD4 = MHC 2/peptide
CD8 = MHC 1/peptide

Question 23

Where does positive selection occur?

Answer 23

In the cortex of the thymus

Question 24

Where does negative selection occur?

Answer 24

In the medulla of the thymus

Question 25

Why do naive CD4 and CD8 T cells migrate to peripheral lymphoid organs?

Answer 25

To look for antigen on MHC class 1 or 2