Exam 2: Dr. Pinchuk TCRs and Antigen Recognition

Question 1

How are PRRs developed?

Answer 1

Germline encoded

Question 2

What kind of specificity do PRRs have?

Answer 2

Broad

Question 3

What do PRRs recognize?

Answer 3

The presence of microbes or tissue damage

Question 4

How is the PRR immune response mediated?

Answer 4

By a variety of cells and molecules that are effective against a wide range of pathogens

Question 5

How are TCRs and BCRs developed?

Answer 5

Gene rearrangement

Question 6

What kind of specificity do TCRs and BCRs have?

Answer 6

High

Question 7

What do TCRs and BCRs recognize?

Answer 7

Specific single molecules

Question 8

What is the TCR and BCR immune response mediated by?

Answer 8

Antigen-specific lymphocytes that are effective against a particular antigen

Question 9

What does it mean if an immune receptor is germline encoded?

Answer 9

Developed during embryogenesis

They don’t change and the don’t recombine

Question 10

What makes a TCR similar to IgR (BCR)?

Answer 10

Heterodimer
Antigen-binding site
V and C domains
The 3D structure of the the extracellular domain resembles the Fab fragment of IgR
The genes encoding the TCR chains have a germline organization similar to BCR light and heavy chains

Question 11

What makes a TCR different from an IgR (BCR)?

Answer 11

No dramatic difference in the size of 2 chains
Always membrane-associated
One antigen-binding site
Antigen recognition function only
No isotype switching of the constant region

Question 12

What does it mean if a receptor is a heterodimer?

Answer 12

It has alpha and beta chains

Question 13

What contributes to TCR diversity?

Answer 13

Gene rearrangement

Small insertion or deletions of nucleotides at the joints between gene segments

Question 14

What does gene rearrangement of TCRs produce?

Answer 14

Sequence variability in the variable regions

Question 15

Does antigen stimulation promote change in the TCR?

Answer 15

No

Question 16

What is somatic hypermutation?

Answer 16

When B cells have a second chance to produce diversity

Question 17

What is T cell development in the thymus initiated by? What does it do?

Answer 17

The assembly of gene segments to make the variable sequence that encodes the V regions of the TCR alpha and beta chains

Question 18

What is the diversity (D) gene segment involved in?

Answer 18

The random rearrangements that produce the TCR beta chain

Question 19

What happens during recombination in TCR diversity?

Answer 19

The DNA between gene segments is deleted from the chromosome

Question 20

Which is more diverse, immunoglobulin or α:β T-cell receptors?

Answer 20

α:β T-cell receptors

Question 21

Which has more variable segments, immunoglobulin or α:β T-cell receptors?

Answer 21

They are both relatively similar, but beta chains have the most

Question 22

Which has more diversity segment, immunoglobulin or α:β T-cell receptors?

Answer 22

Immunoglobulin

Question 23

Which has more V gene pairs, immunoglobulin or α:β T-cell receptors?

Answer 23

α:β T-cell receptors

Question 24

Which has more junction diversity, immunoglobulin or α:β T-cell receptors?

Answer 24

α:β T-cell receptors

Question 25

What do RAG genes provide?

Answer 25

The clonal diversity of T and B cell receptors

Question 26

What do recombinase-activating enzymes encoded by genes RAG-1 and RAG-2 initiate?

Answer 26

V(D)J recombination by nicking double-stranded DNA

Question 27

What do DNA repair proteins do?

Answer 27

Carry out the rejoining process that brings the gene segment of each type together

Question 28

What happens if either of the RAG genes is knocked out?

Answer 28

B and T cell development is completely abolished leading to severe combined immunodeficiency

Question 29

Where have mutations in RAG genes been found?

Answer 29

Human SCID

Question 30

What do mutations in RAG genes that cause partial enzymatic activity give rise to?

Answer 30

An immunodeficiency called Omenn syndrome

Question 31

What is the immunological analysis of Omenn syndrome?

Answer 31

Lymphocytes respond poorly to stimulation No mature B cells and decreased numbers of T cells by FACS analysis Analysis of genomic DNA from peripheral blood lymphocytes reveals T cell oligoclonality suggesting a defect in RAG genes RAG-1 and RAG-2 genes were sequenced and a missense mutation was found in RAG-1 gene

Question 32

What is the immunological analysis of SCID in dogs?

Answer 32

The RAG-1 and RAG-2 genes were sequenced and a missense mutation was found in the RAG-1 gene

Question 33

What do current approaches to hematopoietic stem cell (HSC) gene therapy involve?

Answer 33

The collection and ex vivo manipulation of HSCs

Question 34

What is an alternative approach for correcting blood-related diseases?

Answer 34

The direct intravenous administration of viral vectors, AKA in vivo gene therapy

Question 35

What is the immunological analysis for SCID in horses?

Answer 35

SCID foals are incapable of V(D)J gene rearrangement | DNA protein kinase gene mutation

Question 36

What does expression of TCR on the cell surface require?

Answer 36

Association with additional proteins

Question 37

What is the marker for TCR complex?

Answer 37

CD3

Question 38

What is the function of TCR?

Answer 38

Antigen recognition

Question 39

What is the function of TCR complex?

Answer 39

Antigen recognition and signal transduction

Question 40

What is the difference between alpha-beta chains and gamma-delta chains?

Answer 40

Alpha-beta are specific and adaptive | Gamma-delta are innate immune receptor

Question 41

What does gene rearrangement produce?

Answer 41

Sequence variability in the variable regions

Question 42

Which produces more diversity, alpha-beta chains or gamma-delta chains?

Answer 42

Alpha-beta

Question 43

What is different about gamma-delta chains compared to alpha-beta?

Answer 43

Do nor require antigen processing and MHC presentation of peptide epitopes Express restricted TCR variability CD4 and CD8 are not commonly expressed Rarely contribute to functional memory

Question 44

Where are gamma-delta cells well represented?

Answer 44

Peripheral blood mononuclear cells

Question 45

Where are gamma-delta cells rarely found?

Answer 45

Lymph node parenchyma Spleen Peyer's patches Thymus

Question 46

What percentage of CD3 cells are TCR gamma-delta?

Answer 46

70%

Question 47

What is the diversity of the TCR V region generated by?

Answer 47

Gene recombination and combinatorial association in all species examined to date

Question 48

What percentage of blood lymphocytes in humans have gamma-delta TCRs? In ruminants?

Answer 48

5-15% | 60%

Question 49

Where is the subset of TCRs with more limited receptor diversity found? What kind of role does it have?

Answer 49

In the epidermis of the skin and genital tract | Anti-inflammatory and wound healing role

Question 50

Where is the subset of TCRs with higher receptor diversity found? What does it do?

Answer 50

Secondary lymphoid organs and gut mucosa | Binds to a diverse array of antigens and forms 2 populations, cytokine/chemokine producing and cytotoxic

Question 51

In immature ruminants and pigs, which T cells are the major circulating population?

Answer 51

Gamma-delta

Question 52

Do gamma-delta receptors have MHC restriction? What does this mean?

Answer 52

No | They can perform without MHC