Question 1

In rare instances, B cells can be found that have two immunoglobulin light chain alleles, both of which are rearranged in frame, and can encode functional light chain proteins. Yet, on the surface of the B cell, only one of the two light chain proteins is detected in the membrane-bound immunoglobulin receptor. The reason these rare cells have two functional light chain rearrangements but only express one of the two light chains as part of the B-cell receptor is:

Accepted Answer

The most likely scenario for a B cell with two functional light chain rearrangements but only one expressed in the B-cell receptor is that one of the two light chain proteins doesn't form a stable complex with the heavy chain expressed in this cell. This could be due to amino acid mismatches, differences in affinity or conformation, or simply because the heavy and light chains fail to assemble properly. As a result, the B cell selects the light chain that can form a stable complex with the heavy chain and expresses it on the surface as the B-cell receptor. The other light chain is usually secreted or degraded. The other choices are less likely, as they would either prevent the expression of functional light chains altogether (A, C, D) or affect both light chains equally (E).

Question 2

B-cell receptors and T-cell receptors share a mechanism for generating diversity, and also share overall structural homology both in their V domains and their C domains. This is because the two proteins have nearly identical functions in the immune responses mediated by their respective cell types.

Accepted Answer

While B-cell receptors (BCRs) and T-cell receptors (TCRs) both utilize a mechanism for generating diversity in their variable (V) regions and share structural homology in their V domains, their constant (C) domains and functions in immune responses are different. BCRs are membrane-bound or secreted antibodies that recognize native antigens, whereas TCRs are always membrane-bound and recognize processed antigen fragments presented by major histocompatibility complex (MHC) molecules.

Question 3

For immunoglobulin heavy and light chain genes, and for T-cell receptor $\beta$ chain genes, there are a large number of V gene segments, and relatively few J and/or D segments that rearrange to form the final coding sequence for each gene. The TCR $\alpha$ locus is different in this regard, and this difference is thought to reflect the fact that nearly all $\alpha$:$\beta$ T-cell receptors recognize a peptide bound to an MHC molecule. This unique feature of the T-cell receptor $\alpha$ locus is:

Accepted Answer

The unique feature of the T-cell receptor F1F1F1S1F1F1F10 locus is the presence of over sixty different JF1F1F1S1F1F1F10 gene segments, as opposed to a large number of VF1F1F1S1F1F1F10 gene segments and relatively few J and/or D segments in immunoglobulin heavy and light chain genes and T-cell receptor F1F1F1S1F1F1F10 chain genes. This is thought to reflect the fact that nearly all F1F1F1S1F1F1F10:F1F1F1S1F1F1F10 T-cell receptors recognize a peptide bound to an MHC molecule.

Question 4

An important mechanism for generating diversity in immunoglobulin light chain V-region sequences is based on the fact that the RAG recombinase generates hairpin structures, rather than blunt ends, at the cleavage sites between the recombination signal sequences and the coding sequences. Explain how this mechanism generates diversity at the junctions.

Accepted Answer

The answer of An important mechanism for generating diversity in...

Question 5

For $\alpha$:$\beta$ T-cell receptors, sequence diversity is heavily concentrated at the junctions formed by the rearrangement of gene segments during the generation of the expressed V$\alpha$ and V$\beta$ regions. The result of this organization is to position the most variable part of the T-cell receptor over a certain region of the ligand recognized by this receptor. Which region (outlined in red in Figure ) indicates this part of the ligand recognized by the T-cell receptor?

Accepted Answer

The answer of For $\alpha$:$\beta$ T-cell receptors, sequence diversity is...

Question 6

While B cells and T cells differ markedly in their functions during an immune response, the two lymphocyte subsets share the enzymatic machinery and overall scheme for generating antigen receptor diversity. This is because:

Accepted Answer

Both B cells and T cells require a vast diversity of antigen receptors to recognize and respond to the wide variety of pathogens encountered by the immune system.

Question 7

Antibody diversity is generated by multiple mechanisms, each of which contributes to the generation of antibodies with up to 10¹¹ different amino acid sequences in their antigen-binding sites. Several of these mechanisms involve changes in the DNA sequences encoding the antibody heavy and light chain proteins. One mechanism that does not rely on changes to the DNA within the immunoglobulin heavy and light chain gene loci is, instead, dependent on:

Accepted Answer

The contributions of amino acids from both the heavy chain and the light chain to form the antigen-binding site do not involve changes to the DNA sequences within the immunoglobulin gene loci, but rather rely on the combination of these two chains to create a diverse antigen-binding site.

Question 8

Most of the enzymes involved in immunoglobulin gene rearrangement are ubiquitously expressed in all cells of the body. However, the specific recombination events between V, J, and D gene segments that generate antibody diversity occur only in developing B cells. How do RAG-1 and RAG-2 ensure that recombination takes place at antibody gene segments?

Accepted Answer

The answer of Most of the enzymes involved in immunoglobulin...

Question 9

The different classes of immunoglobulins differ in the sequences of their heavy chain constant regions. As a result, each class of antibody has distinct effector functions. Nonetheless, they are all found at about equal concentrations in the serum of healthy individuals.

Accepted Answer

The different classes of immunoglobulins (IgG, IgM, IgA, IgE, and IgD) do not exist at equal concentrations in the serum. IgG is the most abundant, followed by IgA, IgM, IgD, and IgE, which is present in the least amount.

Question 10

The exon encoding the V region of an immunoglobulin protein is generated by a process of somatic recombination. This recombination event brings V gene and J gene segments together:

Accepted Answer

Somatic recombination of V and J gene segments generates variability in the CDR3 sequence of the V region, which is critical for antigen recognition by immunoglobulins. The other choices are incorrect: A is incorrect because somatic recombination occurs only in B and T cells, not in all cells of the body; C is incorrect because alternative RNA splicing is not involved in the generation of V region sequences; D is incorrect because junctional diversity can be generated by nucleotide additions or deletions; and E is incorrect because the exon encoding the immunoglobulin protein is composed of multiple gene segments, not just the V and J segments.

Question 11

Most eukaryotic genes are encoded in a set of exons that are brought together to form a contiguous protein coding sequence by the process of mRNA splicing. In contrast, immunoglobulin genes use somatic recombination of gene segments and not mRNA splicing to generate the final mRNA that is translated into protein.

Accepted Answer

The answer of Most eukaryotic genes are encoded in a...

Question 12

When first discovered, investigators found it surprising that some single-gene defects causing immunodeficiency syndromes were associated with hypersensitivities to ionizing radiation, thereby leading to increased rates of cancer. The genes accounting for this dual impairment encode ubiquitously expressed DNA repair proteins.

Accepted Answer

This statement is true.

Question 13

Antibodies that bind with high affinity to some viral surface proteins require heavy chain CDR3 loops of unusual length. Whereas the average human heavy chain CDR3 length is ~15 amino acids, antibodies with V_HCDR3 loops of >30 amino acids are readily detected in the repertoire. These antibody heavy chains with CDR3 lengths of >30 amino acids would likely be missing in individuals lacking:

Accepted Answer

Terminal deoxy nucleotidyl transferase (TdT) is responsible for adding non-templated nucleotides (N-regions) to the heavy chain gene segments during V(D)J recombination. This process contributes to the diversity of the antibody repertoire and allows for the generation of antibody heavy chains with CDR3 loops of unusual length, such as those observed in antibodies that bind with high affinity to some viral surface proteins. Therefore, individuals lacking TdT would likely be missing these antibody heavy chains with CDR3 lengths of >30 amino acids.

Question 14

Figure shows the germ-line configuration of three V gene segments (#1, 2, 3), and two J gene segments (#4, 5). Which of the choices below represents a DNA configuration that would result from V-to-J recombination?

Accepted Answer

The V and J gene segments are brought together during VDJ recombination, and the intervening DNA is excised. The resulting DNA configuration has the V and J gene segment attached to one another, with the excised DNA fragment missing. In choice C, V segment 1 is spliced to J segment 5, resulting in a joined DNA sequence, with the intervening fragment removed.

Question 15

Some pathogenic microorganisms encode proteins, such as the Staphylococcus Protein A, that bind to immunoglobulin constant region domains with high affinity. These microbial proteins provide a benefit to the microorganism by:

Accepted Answer

Preventing antibodies bound to the microbe from binding to Fc receptors on phagocytes is a strategy used by some pathogens, like Staphylococcus aureus with its Protein A, to evade the immune system. By binding to the Fc region of antibodies, these microbial proteins prevent the antibodies from interacting with Fc receptors on immune cells like phagocytes, thereby inhibiting opsonization and phagocytosis.

Question 16

Recombination signal sequences are conserved heptamer and nonamer sequences that flank the V, J, and D gene segments which undergo recombination to generate the final V region coding exon. Some of these have 12-nucleotide spacers between the heptamer and nonamer, and others have 23-nucleotide spacers. The reason recombination signal sequences come in these two forms is:

Accepted Answer

The 12/23 rule ensures that recombination occurs between segments with different spacer lengths, preventing inappropriate recombination events such as V_H to V_H.

Question 17

Different individuals can have different numbers of functional V gene segments as well as different numbers of constant region genes. This type of genetic polymorphism between individuals indicates that:

Accepted Answer

The answer of Different individuals can have different numbers of...

Question 18

Some T cells express $\gamma$:$\delta$ T-cell receptors rather than $\alpha$:$\beta$ T-cell receptors. The organization of the $\alpha$  locus and the $\delta$ locus helps to ensure that each T cell cannot express both types of T-cell receptors. The mechanism involved is that:

Accepted Answer

The rearrangement of the T-cell receptor α gene (represented here as F1F1F1S1αF1F1F10) involves deletion of the δ locus (F1F1F1S1δF1F1F10) on the same allele, ensuring that a T cell cannot express both α:β and γ:δ T-cell receptors.

Question 19

IgM is the first antibody isotype secreted following activation of a naive B cell. IgM is found at high concentrations in the serum, and is found as a very high molecular weight complex. This high molecular weight complex is composed of:

Accepted Answer

IgM is found as a pentamer (which is a high molecular weight complex) composed of five IgM monomers held together by disulfide bonds and a J chain.

Question 20

The addition and subtraction of nucleotides at the junctions between V, D, and J gene segments creates antibody proteins with wide variations in the numbers of amino acids in their CDR3 regions. This variability in CDR3 length is important as:

Accepted Answer

The answer of The addition and subtraction of nucleotides at...

Quiz 5: The Generation of Lymphocyte Antigen Receptors

B-cell receptors and T-cell receptors share a mechanism for generating diversity, and also share overall structural homology both in their V domains and their C domains. This is because the two proteins have nearly identical functions in the immune responses mediated by their respective cell types.

While B cells and T cells differ markedly in their functions during an immune response, the two lymphocyte subsets share the enzymatic machinery and overall scheme for generating antigen receptor diversity. This is because:

The different classes of immunoglobulins differ in the sequences of their heavy chain constant regions. As a result, each class of antibody has distinct effector functions. Nonetheless, they are all found at about equal concentrations in the serum of healthy individuals.

The exon encoding the V region of an immunoglobulin protein is generated by a process of somatic recombination. This recombination event brings V gene and J gene segments together:

Figure shows the germ-line configuration of three V gene segments (#1, 2, 3) , and two J gene segments (#4, 5) . Which of the choices below represents a DNA configuration that would result from V-to-J recombination?

Some pathogenic microorganisms encode proteins, such as the Staphylococcus Protein A, that bind to immunoglobulin constant region domains with high affinity. These microbial proteins provide a benefit to the microorganism by:

Different individuals can have different numbers of functional V gene segments as well as different numbers of constant region genes. This type of genetic polymorphism between individuals indicates that:

Some T cells express $\gamma$ : $\delta$ T-cell receptors rather than $\alpha$ : $\beta$ T-cell receptors. The organization of the $\alpha$ locus and the $\delta$ locus helps to ensure that each T cell cannot express both types of T-cell receptors. The mechanism involved is that:

IgM is the first antibody isotype secreted following activation of a naive B cell. IgM is found at high concentrations in the serum, and is found as a very high molecular weight complex. This high molecular weight complex is composed of:

The addition and subtraction of nucleotides at the junctions between V, D, and J gene segments creates antibody proteins with wide variations in the numbers of amino acids in their CDR3 regions. This variability in CDR3 length is important as:

Quiz 5: The Generation of Lymphocyte Antigen Receptors

B-cell receptors and T-cell receptors share a mechanism for generating diversity, and also share overall structural homology both in their V domains and their C domains. This is because the two proteins have nearly identical functions in the immune responses mediated by their respective cell types.

While B cells and T cells differ markedly in their functions during an immune response, the two lymphocyte subsets share the enzymatic machinery and overall scheme for generating antigen receptor diversity. This is because:

The different classes of immunoglobulins differ in the sequences of their heavy chain constant regions. As a result, each class of antibody has distinct effector functions. Nonetheless, they are all found at about equal concentrations in the serum of healthy individuals.

The exon encoding the V region of an immunoglobulin protein is generated by a process of somatic recombination. This recombination event brings V gene and J gene segments together:

Figure shows the germ-line configuration of three V gene segments (#1, 2, 3) , and two J gene segments (#4, 5) . Which of the choices below represents a DNA configuration that would result from V-to-J recombination?

Some pathogenic microorganisms encode proteins, such as the Staphylococcus Protein A, that bind to immunoglobulin constant region domains with high affinity. These microbial proteins provide a benefit to the microorganism by:

Different individuals can have different numbers of functional V gene segments as well as different numbers of constant region genes. This type of genetic polymorphism between individuals indicates that:

Some T cells express γ\gammaγ : δ\deltaδ T-cell receptors rather than α\alphaα : β\betaβ T-cell receptors. The organization of the α\alphaα locus and the δ\deltaδ locus helps to ensure that each T cell cannot express both types of T-cell receptors. The mechanism involved is that:

IgM is the first antibody isotype secreted following activation of a naive B cell. IgM is found at high concentrations in the serum, and is found as a very high molecular weight complex. This high molecular weight complex is composed of:

The addition and subtraction of nucleotides at the junctions between V, D, and J gene segments creates antibody proteins with wide variations in the numbers of amino acids in their CDR3 regions. This variability in CDR3 length is important as:

Some T cells express $\gamma$ : $\delta$ T-cell receptors rather than $\alpha$ : $\beta$ T-cell receptors. The organization of the $\alpha$ locus and the $\delta$ locus helps to ensure that each T cell cannot express both types of T-cell receptors. The mechanism involved is that: