T and B cell Development

Question 1

What are the components of a TCR?

Answer 1

2 polypeptide chains, one alpha, on beta OR one gamma and one delta; They are not isotypes. T cells do NOT change their TCRs and they are not secreted.

Question 2

Do both CD4 and CD8 cells have alpha/beta TCRs?

Answer 2

YES

Question 3

Do gamma/delta TCRs bind to MHC 1 or 2?

Answer 3

NO

Question 4

What is the goal of TCR production?

Answer 4

To produce a TCR alpha or beta chain polypeptide with 2 regions; Variable region and a constant region.

Question 5

Describe the problem and solution to TCR production.

Answer 5

Germline DNA contains exons that encode the constant regions but does NOT contain exons that encode variable regions. Therefore, DNA is rearranged to form an exon that will encode a specific variable region.

Question 6

What is required in TCR production?

Answer 6

1. Enzymes that can cut, bend and repair DNA; RAG, Tdt, DNA-PK and other enzymes.
2. Specific regions of DNA that can be manipulated; V, D and J gene segments.

Question 7

What genes are needed to make the beta chain?

Answer 7

V, D, J make the variable region. C makes the constant region.

Question 8

What genes are needed to make the alpha chain?

Answer 8

V and J make the variable region. C makes the constant region.

Question 9

What does RAG1 and 2 do?

Answer 9

They bind to the gene segments, cut the DNA, and join the gene segments together; Without these enzymes, antibody and TCR can not be made nor can mature B and T cells.

Question 10

What does TdT do?

Answer 10

It adds random nucleotides (N nucleotides) to the ends of gene segments that have been cut by RAG before the gene segments are attached together; Active in pro-B and pro-T cells; Adds junctional diversity.

Question 11

What is the role of DNA repair enzymes?

Answer 11

They help seal the junctions; Can change nucleotide sequence at junctions during repair. (Junctional Diversity)

Question 12

What is the benefit of cutting and rearranging DNA for TCRs?

Answer 12

Random combinations of V, D, and J gene segments and junctional diversity increase the chance that we will produce a B or T cell with an antigen receptor that is specific for the pathogenic antigens we are exposed to.

Question 13

What are the two functional requirements of a T cell?

Answer 13

1. It must have a TCR that will bind to MHC

2. It must have a TCR that will NOT bind to self antigens.

Question 14

When is the decison point between becoming a CD4 or CD8?

Answer 14

The decision is not made until the transition from an immature T cell to a mature T cell.

Question 15

KNOW the T cell development chart

Answer 15

ON page 61.

Question 16

What is the disadvantage to random VDJ rearrangement?

Answer 16

Reactivity to Self

Question 17

What happens to an autoreactive B or T cell?

Answer 17

1. Destroy the autoreactive cell.
2. Change the autoreactive cell.
3. Suppress the autoreactive cell.

Question 18

Explain Central tolerance vs Peripheral tolerance.

Answer 18

The repression of autoreactive cells in the bone marrow or thymus (Central tolerance). If its in the lymphoid tissues/organs (peripheral tolerance)

Question 19

Describe the components of an antibody molecule.

Answer 19

Made of 4 polypeptide chains: 2 identical heavy chains and 2 identical light chains that are connected by disulfide bonds.

Question 20

Describe the makeup of a heavy chain.

Answer 20

One variable region (VH); contains amino acids that bind to a specific epitope on an antigen. Also has a constant region; Determines effector function of antibody.

Question 21

What is an epitope?

Answer 21

A specific region of an antigen that antibodies (or TCR) bind.

Question 22

What are the different types of heavy chain?

Answer 22

Mew, delta, gamma, alpha, epsilon; Each individual antibody molecule has one type.

Question 23

Describes the components of the light chain.

Answer 23

One variable (VL) and on constant (CL) region; Two different types of light chain, kappa and lambda. Each individual antibody molecule has one type.

Question 24

What does the Fc region do?

Answer 24

It determines the antibody’s isotype. All antibodies have a kappa or lambda connected to a mew, delta, gamma, alpha or epsilon heavy chain; This makes IgM, D, G, A, or E respectively.

Question 25

What is the goal of antibody production?

Answer 25

To produce an antibody light chain (or heavy chain) polypeptide with 2 regions; A variable and constant region.