8 - Adapt 2: Innate-Adaptive (T Cell) Interaction

Question 1

CD4 T-cells are also known as ______ T-cells and have MHC ___

Answer 1

Helper; 2

Question 2

CD8 T-cells are also known as ______ T-cells and have MHC ___

Answer 2

Cytotoxic; 1

Question 3

What do T-cells use T-cell receptors (TCR’s) for?

Answer 3

To help them “see” the antigen

Question 4

CD8 and CD4 are _______

Answer 4

Coreceptors

Question 5

What is the purpose of having coreceptors?

Answer 5

To stabilize the complex interactions of the TCR

Question 6

What are the majority of TCR’s composed of?

Answer 6

alpha and beta chains

Question 7

What is CD3?

Answer 7

A coreceptor on the alpha-beta TCR

Question 8

What does ITAM stand for?

Answer 8

Immune-mediated Tyrosine-based Activation Motif

Question 9

What differs on TCR’s that determines which peptide (antigen) it can bind?

Answer 9

Complementarity Determining Region (CDR)

Question 10

What two structures do TCR’s associate with that help propagate signals?

Answer 10

CD3 (coreceptor) and zeta chains

Question 11

How can TCR’s recognize so much diversity in antigens?

Answer 11

Different CDR’s!

Question 12

What is a T-cell receptor gene?

Answer 12

T-cell receptor protein that can recognize virtually all the potential AA sequences in a peptide

Question 13

What is the big problem with the TCR gene?

Answer 13

The genome is too small to encode all the genes needed to code for the diversity of antigens

Question 14

What are the two theories about how TCR diversity is generated?

Answer 14

-Modified germ-line theory
-Somatic hypermutation theory

Question 15

Which TCR diversity theory is likely to be true?

Answer 15

Both!
Each TCR molecule is encoded by multiple, germ-line, variable-region gene segments, which are rearranged differently and randomly in each naive immune cell to produce a diverse primary receptor repertoire (done pre-birth)

Question 16

What are the 4 segments in TCR genes?

Answer 16

-Variable (V)
-Diversity (D)
-Joining (J)
-Constant (C)

Question 17

Which segments does the alpha chain have?

Answer 17

V and J

Question 18

Which segments does the beta chain have?

Answer 18

V, D, and J

Question 19

What is VDJ recombination?

Answer 19

Gene recombination that joins random copies of each segment together

Question 20

Which genes mediate VDJ recombination?

Answer 20

RAG1 and RAG2 (recombination activating genes)

Question 21

How do RAG1/2 function?

Answer 21

They will randomly bind to a single gene on the alpha or beta chain and then join that with another gene segment and it will bring the two segments together. This will create a hairpin loop that will get spliced out. In the beta chain, this new double segment will then be linked with another segment (because beta is VDJ and alpha is only VJ)

Question 22

What is TdT?

Answer 22

Terminal Deoxynucleotidyl Transferase. Randomly adds nucleotides to join spliced ends of the alpha/beta chains

Question 23

What can TdT introduce?

Answer 23

Mutations

Question 24

What enzyme cleaves out hairpin loops from from the recombined chain?

Answer 24

DNA-dependent protein kinase

Question 25

Where is the variation in each TCR alpha/beta chain introduced

Answer 25

In CRD3! *Know this cause its highlighted in red twice so probably important

Question 26

Where does screening of good TCR’s occur?

Answer 26

Thymus stroma, then migrates to thymus medulla (done before birth)

Question 27

What is -/- selection?

Answer 27

Cell has no CD4 or CD8

Question 27

What is +/+ selection?

Answer 27

Cell has both CD4 and CD8

Question 27

What is +/- selection?

Answer 27

Cell has either CD4 or CD8

Question 28

What happens to T-cells with a non-functional TCR?

Answer 28

Destroyed

Question 29

What happens to T-cells with a self-reactive TCR

Answer 29

DESTROYED

Question 30

What happens to T-cells with a non-self reactive TCR

Answer 30

Allowed to live :) goes to periphery

Question 31

What 2 things occur during T-cell development and what is the result?

Answer 31

-Positive selection of functional T-cells via CD4, CD8 and MHC recognition
-Negative selection of self-reactive T-cells
*Results in naive T-cells (1-4%)

Question 32

What type of cells is negative selection mediated by?

Answer 32

Macrophages and dendritic cells

Question 33

How are T-cells positively selected?

Answer 33

The TCR will have a preference for MHC1 or MHC2 and then will just lose expression of the unused CD4 or CD8

Question 34

What type of cells do developing T-cells bind to during positive selection to recognize an MHC complex?

Answer 34

Epithelial antigen presenting cells (cortical and medullary epithelial cells)

Question 35

What happens to the beta chain after recombination?

Answer 35

It moves to the surface of the cell and binds the pre-alpha chain, which makes the whole thing a pre-TCR

Question 36

What does the pre-TCR do?

Answer 36

Tests if the cell can signal, and if it can then it makes the alpha chain and forms a complex with CD3 and zeta chain

Question 37

What happens if the TCR is bound to MHC1?

Answer 37

Will express CD8, will cease to express CD4

Question 38

What happens if the TCR is bound to MHC2?

Answer 38

Will express CD4, will cease to express CD8

Question 39

Do CD4 and CD8 contribute to antigen specificity of the TCR?

Answer 39

NO

Question 40

What leads to activation of a T-cell via signals transduced through the CD3 complex of molecules?

Answer 40

Combination of TCR and CD4 or CD8 binding

Question 41

What “educates” T lymphocytes?

Answer 41

Thymocytes. Teaches to differentiate self vs non-self

Question 42

What is AIRE?

Answer 42

Auto-immune regulator gene

Question 43

What does AIRE do?

Answer 43

Expresses proteins within the thymus so self-reactive T-cells are negatively selected

Question 44

Why does a mutation in DNA-dependent phosphokinase (a DNA repair gene) lead to Arabian foals not being able to control infections? What is this disease called?

Answer 44

Called Severe Combined Immunodeficiency Disease (SCID). The mutated gene is responsible for re-ligation of cut DNA, so it can’t make functional TCR’s.