T Cell Receptors- L8

Question 1

CD8 positive T cells target:

Answer 1

A virus infected cell

Question 2

CD4 positive T cells role

Answer 2

Interact with macrophages to produce cytokines and also interact with B cells to produce cytokines. Can signal a B cell to terminally differentiate into a plasma cell.

Question 3

T cell receptor composition

Answer 3

• Alpha chain and beta chain
• Variable region
• Constant region
• Transmembrane region and cytoplasmic tail

Question 4

Biochemical characterization of TCR

Answer 4

1. Disulfide linked heterodimer
2. Both chains are glycoproteins
3. Transmembrane protein only. NO soluble form.
4. Constant and variable regions

Question 5

CD3 role in TCRs

Answer 5

Important in binding TCR to the membrane. They are closely related. The TCR-CD3 complex can participate is signal transduction events.

Question 6

Generating a diverse TCR Repertoire mechanisms

Answer 6

• Recombination of different gene segments (VDJ)
• Recombination of numbers of gene segments (TCRdelta locus)
• Imprecise joining of gene segments
• P and N nucleotide addition (TdT)
• Assembly of different combinations of rearranged TCR chains (alpha and beta or gamma and delta)
• NO somatic mutations!!!!!!!!

Question 7

Components of alpha:beta TCRs

Answer 7

• Variable segments in both
• Diversity segments only in beta chain
• Joining segments in both
• Overall higher diversity in TCR than in BCR

Question 8

Alpha:beta TCRs recognize:

Answer 8

-Short peptide fragments generated from antigenic proteins presented by MHC molecules

Question 9

MHC class 1 molecule

Answer 9

• Most variability occurs in groove region
• Alpha chain is not covalently associated with beta chain.
• Beta chain stabilizes alpha chain on the surface of the cell.

Question 10

MHC class 2 molecule

Answer 10

• Longer peptides than class 1
• Most polymorphism in the beta1 domain.
• NO polymorphism in the alpha2 or beta2 domain.
• Beta is covalently associated unlike class 1

Question 11

Requirements for recognition by a T cell

Answer 11

TCR must see the antigen plus a non-foreign MHC

Question 12

MHC class 1 expression

Answer 12

• All nucleated cells in the body

- Present to CD8 positive T cells

Question 13

MHC class 2 expression

Answer 13

• Antigen presenting cells

- Present to CD4 positive T cells

Question 14

Cytosolic pathogens

Answer 14

• Bind to MHC class 1
• Presented to CD8 T cells
• Causes death of the presenting cell

Question 15

Intravesicular pathogens

Answer 15

• Bind to MHC class 2
• Presented to CD4 T cells
• Activation to kill intravesicular bacteria and parasites

Question 16

Extracellular pathogens and toxin

Answer 16

• Degraded in endocytic vesicles
• Bind to MHC class 2
• Presented to CD4 T cells
• Activates B cells to secrete Ig to eliminate extracellular bacteria and toxins

Question 17

Processing of antigen by class 1 MHC

Answer 17

• Newly synthesized proteins are ubiquinated, then fragmented into peptides by the proteasome
• Peptides attach to TAP protein in the membrane of the ER
• Complex moves into the lumen of the ER and peptide is place in binding groove of MHC class 1
• Peptide travels to cell surface

Question 18

Processing of antigen by class 2 MHC

Answer 18

• Ingested antigens are taken into phagolysosome and fragmented by proteases
• Peptides move to endosomal compartments and placed in binding groove of MHC class 2
• CLIP is displaced and the the complex is carried to the cell surface
• Note: CLIP binds MHC class 2 to prevent the binding of self-peptide fragments

Question 19

Superantigens

Answer 19

• Can act as bridge between TCR and MHC and stimulate high percentage of T cells bearing certain V genes
• Bacterial enterotoxins, minor lymphocyte stimulating antigens, unidentified endogenous antigens
• No requirements for recognition of a peptide
• Ex: toxic shock syndrome is so devastating because it activates so many T cells so quickly