1.5 T-Cell Diversity

Question 1

The T-cell is a 2 component membrane bound molecule. What are those components?

Answer 1

Alpha and beta chain with a variable and constant region

Question 2

TCR requires additional ___ to enable signaling

Answer 2

Proteins

Question 3

What are the types of additional proteins?

Answer 3

CD3 contains an Epsilon (ε) and Delta (δ)
CD3 contains and Epsilon (E) and Gamma (γ)

Question 4

What 2 events occur for the formation of T-cell receptor proteins in both the alpha and beta chain?

Answer 4

Somatic recombination and the formation of T cell receptor genes

Question 5

What regions does the alpha chain have?

Answer 5

Joining, variable and constant regions

Question 6

What regions does the beta chain have?

Answer 6

Variable, diversity, joining, and constant regions

Question 7

Recognition of antigen by T cell requires the ___

Answer 7

MHC molecule
- T cells DON’T bind free antigens

Question 8

CD8 binds the ___ domain of ___

Answer 8

alpha 3
MHC class I

Question 9

CD4 binds the ___ domain of ___

Answer 9

Beta 2
MHC class II

Question 10

What must interact with a MHC molecule for T cell stimulation?

Answer 10

TCR and co-receptor

Question 11

CD4 T cell coreceptors are

Answer 11

D1, D2, D3, and D4

Question 12

CD8 T cell coreceptors are

Answer 12

alpha and beta

Question 13

Describe CD8 T cell interaction with a virally infected cell

Answer 13

1. Antigen present on surface of MHC class I
2. T cell recognizes the antigen because of MHC I and the coreceptor on the T cell
3. T cell is stimulated for apoptosies

Question 14

Describe CD4 T cell interaction with a macrophage

Answer 14

1. Antigen presented on surface of MHC class II
2. T cell with coreceptor recognizes it and it stimulates the production of cytokines that act on the macrophage to activate it and kill
3. Cytokines are released from macrophage and go into blood to attract more phagocytes

Question 15

Describe CD4 T cell interaction of B cell

Answer 15

1. Antigen presented on surface of MHC II on B cell
2. T cell releases cytokines that stimulates the B cell to turn into plasma cell
3. Plasma cell secretes antibodies

Question 16

What’s the region called that binds the peptide?

Answer 16

Peptide binding groove

Question 17

MHC antigens are small ___ peptides

Answer 17

Linear

Question 18

Describe the linear peptides presented by MHC I

Answer 18

• They’re 8-10 amino acids long
• Both ends are firmly attached to MHC I molecule

Question 19

Describe the linear peptides presented by MHC II

Answer 19

• 12-15 amino acids long
• Both ends are floppy

Question 20

Steps for extracellular antigen binding to MHC class II

Answer 20

1. Extracellular antigen is taken in by endocytotic vesicle
2. Phagolysosome chews up the antigen and peptides form
3. MHC is released from ER and golgi and binds to antigen
4. MHC class II presents peptide at cell surface

Question 21

What is the invariant chain?

Answer 21

A peptide that’s stuck onto the antigen binding region on the MHC class II and prevents molecules from binding to the antigen binding region

Question 22

Steps for removing a invariant chain

Answer 22

1. Invariant chain blocks antigen binding region on MHC class II in ER
2. Placed into vesicle and goes to cytosol
3. Invariant chain is cleaved and CLIP fragment’s left
4. HLA-DM releases CLIP and allows MHC II to bind antigens

Question 23

Peptides produced in the cytosol are transported to the ___ in virally infected cells

Answer 23

ER

Question 24

Steps for transporting peptides from viruses into the ER

Answer 24

1. Proteosome chews up the proteins from virus
2. Peptide fragments form
3. TAP (transporter associated w/ antigen processing) transports the peptides from cytosol to ER

Question 25

MHC class I is stabilized by ___ until ___ binds. Why does it do this?

Answer 25

Calnexin beta2-microglobulin Keeps MHC I inactive and prevents it from binding things

Question 26

Steps for intracellular pathogen binding to MHC class I

Answer 26

1. Calnexin stabilizes MHC I until beta2-macroglobulin binds 2. beta2-macroglobulin binds to MHC I and calnexin leaves 3. beta2-macroglobulin forms the peptide loading complex with calreticulin, tapasin, TAP, ERp57, and PDI 4. TAP brings in a peptide and it binds to MHC I making it mature MHC I 5. MHC class I dissociates from peptide loading complex and leaves ER

Question 27

What happens if the peptide is too long for MHC class I?

Answer 27

ERAP removes N-terminal AA to give peptide 8-10 AA

Question 28

Tissue specificity for MHC Class II

Answer 28

Antigen presenting cells and thymic epithelium - B cells, macrophages, and dendrites

Question 29

Tissue specificity for MHC Class I

Answer 29

T cells, B cells, macrophages, dendritic cells, and neutrophils

Question 30

What is MHC called in humans?

Answer 30

Human Leucocyte Antigens

Question 31

Human MHC Class I isotypes and what is their morphology?

Answer 31

HLA-A (highly polymorphic) HLA-B (highly polymorphic) HLA-C (highly polymorphic) HLA-E (oligomorphic) HLA-F (monomorphic) HLA-G (oligomorphic)

Question 32

Human MHC Class II isotypes and what is their morphology?

Answer 32

HLA-DM (oligomorphic) HLA-DO (Oligo and monomorphic) HLA-DP (polymorphic) HLA-DQ (polymorphic) HLA-DR (highly polymorphic and oligomorphic)

Question 33

What is the possible number of alleles for homozygotes?

Answer 33

3 Class I genes and 3 Class II genes

Question 34

What is the possible number of alleles for heterozygotes?

Answer 34

6 Class I genes and 16 Class II genes

Question 35

Describe intrallelic conversion

Answer 35

1 allele from maternal and 1 from paternal --> highly homologous genes allow for crossing over and now you have new allotype

Question 36

Describe gene conversion

Answer 36

DNA fragment loops around and you get a new cross section - Gene conversion from the same chromosome

Question 37

All variability in MHC is located where?

Answer 37

peptide binding groove

Question 38

T/F: TCR must recognize the MHC marker and the antigen in context with the MHC marker

Answer 38

True

Question 39

What are the 2 classes of T-cell receptors?

Answer 39

alpha:beta T cell γ(gamma):δ(delta) T cell

Question 40

γ(gamma):δ(delta) T cell

Answer 40

- In the gut epithelium tissue - At a lower concentration - Don't display MHC restriction - 5% of T cells - Respond quickly

Question 41

Steps for transposase activity:

Answer 41

1. Transposase cleaves a gene encoding a receptor of innate immunity 2. Inserted transposon splits receptor gene into 2 segments 3. Chromosomal rearrangements move transposase genes to different chromosome