HRR: antigen recognition in the adaptive immune system

Question 1

Describe the difference between B-cell antigen receptors and T-cell antigen receptors

Answer 1

B-cell antigen receptors are membrane bound and can recognize whole proteins, peptides, polysaccharides, lipids, nucleic acids, and small chemicals. T-cell antigen receptors are T-cell receptors and can only recognize short peptide antigens displayed by major histocompatibility complex (MHC)

Question 2

What is a complementarity determining region

Answer 2

They’re found at the tip of the variable region on antibodies. They interact with the antigen and make it so different antibodies bind to different things

Question 3

What does papain do to antibodies?

Answer 3

Cuts them into Fab and Fc. The Fab region takes part in monovalent antigen binding and is very similar to T cell receptors structurally!

Question 4

What does pepsin do to antibodies?

Answer 4

Cuts them into F(ab’)2 small fragments, which take part in bivalent binding to antigens. It can bind two of the same things at the same time!

Question 5

All B cell receptors are encoded by which 3 genes

Answer 5

Heavy chain, kappa light chain, and lambda light chain

Question 6

All T cell receptors are encoded by which 2 genes

Answer 6

Alpha chain and beta chain

Question 7

Describe what VDJ recombination is, and the multiple ways that it generates
diversity of antigen receptors on lymphocytes.

Answer 7

Each gene associated with B and T cell receptors have many exons for variable regions, meaning there are many choices to make the actual antigen receptor. The heavy and beta chains have VDJ, while the alpha and light chains have VJ. In the final antigen there will only be one each of V, D, and J. the presence of many options allows for diversity of antigen receptors

Question 8

Describe the role of VDJ recombinase

Answer 8

An enzyme that cleaves DNA at recognition sequences at the ends of V, D, and J segments and repairs the breaks with ligases.

Question 9

How does VDJ recombinase decide which segments to join together?

Answer 9

The segments that get joined by ligase are random, and the alleles used in the final receptor are also random. This allows for combinatorial diversity

Question 10

What is junctional diversity?

Answer 10

Ligases add random numbers of nucleotides to the join sites during VDJ recombination. This provides a large amount of variability

Question 11

What does VDJ recombinase require to work? What happens if someone does not have them?

Answer 11

RAG-1 and RAG-2. If someone doesn’t have these, they cannot properly make functional B and T cells and will be immunodeficient

Question 12

What are the 3 steps for lymphocyte maturation

Answer 12

-Proliferation of immature cells
-Expression of antigen receptor genes
-Selection of lymphocytes that have useful receptors

Question 13

Describe the progression from pro-, pre-, immature and mature lymphocytes in terms of order, antigen receptor expression, and positive and negative selection

Answer 13

-A pro T/B cell proliferates in response to IL7
-Pre-B/T cell expresses one chain of an antigen receptor. If it fails to express the receptor the cell will die
-The pre-T/B cells proliferate in response to IL7
-Immature B/T cells express their complete antigen receptor
-Positive or negative selection occurs (able to function vs being eliminated)
- mature B/T cell is formed!

Question 14

True or false: all receptor molecules on a given B or T cell are identical

Answer 14

True! There is variation among B and T cells, but the individual cells must have identical receptor molecules

Question 15

How many constant region genes are present for light chains? Heavy chains?

Answer 15

Light chains have 1, heavy chains have 9

Question 16

What is special about mature naïve b cells?

Answer 16

They have IgM and IgD on their cell surfaces at the same time. They are the only cell that has this. This is because IgM and IgD have the same antigen binding specificity

Question 17

Which antibody classes exist as monomers?

Answer 17

IgD, IgE, IgG

Question 18

which antibody classes exist as dimers?

Answer 18

IgA

Question 19

which antibody classes exist as pentamers?

Answer 19

IgM

Question 20

what is the purpose of allelic exclusion?

Answer 20

It exists in order to ensure only one heavy, and one light chain gene get expressed in each mature B or T cell; once one gives a signal, the other gets silenced to avoid its rearrangement and expression

Question 21

Describe allelic exclusion in B cell receptors

Answer 21

-First heavy chain undergoes VDJ rearrangement

-If this rearrangement is non-productive, a 2nd heavy chain undergoes VDJ rearrangement. If it is productive, the first kappa light chain undergoes rearrangement

-Subsequent kappa light chain followed by lambda light chains (4 total) will undergo rearrangement.

-If the 1st and 2nd heavy chain rearrangements both prove to be non-productive and the light chains fail, the cell will die.

Question 22

What is the last test for mature B cells to prevent autoimmune disease

Answer 22

They interact with self-proteins on stromal cells. If there is weak binding, the cell is positively selected and IgD and IgM are expressed. If there is strong binding, the cell will be deleted via apoptosis

Question 23

Describe allelic exclusion in T cell receptors

Answer 23

-Pro-T cells recombine one beta chain gene.

-If the beta chain gene recombination is productive, the alpha chain gene will undergo recombination

-If both alpha and beta are productive, CD4 and CD8 are induced

Question 24

Describe allelic exclusion in T cell receptors

Answer 24

-Pro-T cells recombine one beta chain gene.

-If the beta chain gene recombination is productive, the other is silenced and the alpha chain gene will undergo recombination

-If both alpha and beta are productive, CD4 and CD8 are induced

Question 25

how is a T cell’s fate determined?

Answer 25

Recognition of MHC and peptides is tested. Positive selection occurs first in the cortex, then negative selection occurs in the medulla of the thymus.

Question 26

describe determination of the 4 T cell fates

Answer 26

-Weak binding between class II MHC and a peptide will lead to CD4 expression.

-Weak binding between class I MHC and a peptide will lead to CD8 expression

-No recognition of MHC and peptide will lead to death of the cell

-If there is a strong recognition of either, the cell dies.

Question 27

Explain what a double positive T-cell is and where and when they appear in T-
cell maturation

Answer 27

A double positive T cell expressed both CD8 and CD4. It occurs while the T cell is immature in the thymus

Question 28

Explain the relationship of BCR and TCR to continuous and discontinuous/
conformational epitopes

Answer 28

BCR: can see continuous/discontinuous epitopes

TCR: can only see continuous epitopes

Question 29

describe B1 cells

Answer 29

derived from fetal liver; only have IgM and contain CD5. They’re thought to protect us from bacteria moving across our gut wall and into the bloodstream

Question 30

describe marginal B cells

Answer 30

they have CD21 instead of IgM/IgD. They’re primarily in the spleen and protect us from things in the blood

Question 31

where are B2 cells derived from?

Answer 31

the bone marrow