Question 1

MHC class I surface expression is dependent on an abundant source of pathogen-derived peptides. Thus, in uninfected cells, nearly all of the MHC class I proteins are degraded and never reach the cell surface.

Accepted Answer

MHC class I molecules are expressed on the surface of nearly all nucleated cells regardless of infection status, presenting endogenously derived peptides (including self peptides) to the immune system, not solely pathogen-derived peptides.

Question 2

Multiple mechanisms contribute to create a wide diversity in MHC protein expression between different individuals in the population. In addition to the genetic polymorphism of MHC genes, what additional mechanism(s) contribute to this diversity?

Accepted Answer

Polygeny and co-dominant expression of MHC proteins.
The high polymorphism of the classical MHC genes ensures diversity in MHC gene expression in the population as a whole. However, no matter how polymorphic a gene is, no individual can express more than two alleles at a single gene locus. Polygeny, the presence of several different related genes with similar functions, along with the co-dominant expression of both alleles of each MHC gene, ensures that each individual produces a number of different MHC molecules. The combination of polymorphism, polygeny, and co-dominant expression produces the diversity of MHC molecules seen both within an individual and in the population at large.

Question 3

Three major cell types, dendritic cells, macrophages, and B cells, present peptides bound to MHC class II molecules for recognition by CD4 T cells. In general, these peptides are derived from proteins or pathogens taken up by the cell by endocytosis, phagocytosis, or macropinocytosis. Based on these pathways of antigen uptake, some of the enzymes that degrade proteins to generate peptides for MHC class II presentation are:
A) Ubiquitin ligases that tag proteins for degradation by the proteasome
B) ATP transporter proteins that deliver endocytic proteins into the cytosol for degradation
C) Cysteine proteases like cathepsins that function at acidic pH
D) The lysosomal thiol reductase found in the endosomes
E) The lysosome-associated membrane trafficking protein, LAMP-2

Accepted Answer

Cysteine proteases like cathepsins function at acidic pH, which is found in endosomes and lysosomes where antigen degradation occurs. These enzymes are involved in protein degradation to generate peptides for MHC class II presentation.

Question 4

The experiment shown in Figure uses two strains of mice that differ in their MHC genes. Strain A is H-2^aand Strain B is H-2^b. Mice of each strain are infected with the virus LCMV, and T cells are isolated at day 8 post-infection. These T cells are mixed with target cells that express either H-2^aor H-2^b; in each case, the target cells are either uninfected or infected with LCMV. After a four-hour incubation of T cells with target cells, the percentage of target cells lysed by the T cells is shown in the graph. The explanation for the results of this experiment is: A) Mice of strain B do not make a T cell response to LCMV. B) Mice of strain A make a more robust T cell response to LCMV than mice of strain B. C) Target cells that express H-2^b cannot be infected with LCMV. D) T cells from mice of strain A only recognize viral peptides on target cells expressing H-2^a. E) LCMV peptides do not bind to MHC class I molecules from H-2^b mice.

Accepted Answer

The answer of The experiment shown in Figure uses two...

Question 5

The MARCH-1 E3-ubiquitin ligase is expressed in B cells, dendritic cells, and macrophages. The pathway regulated by MARCH-1 is targeted by some pathogens in an immune evasion strategy. In this strategy, the pathogens encode:
A) A protein that induces degradation of MARCH-1
B) A protein that mimics MARCH-1 and functions similarly
C) A protein that binds to MARCH-1 and inhibits its function
D) A protein that is induced by IL-10 in macrophages and dendritic cells
E) A protein that induces degradation of CD86

Accepted Answer

The answer of The MARCH-1 E3-ubiquitin ligase is expressed in...

Question 6

In a mixed lymphocyte reaction, T cells from individual A make a robust response to antigen-presenting-cells from individual B, as long as the two individuals express different alleles of MHC molecules. Estimates indicate that up to 10% of the T cells from individual A may contribute to this response. If one performed this assay using responder T cells from a child and antigen-presenting cells from one parent, the result would be:
A) A massive proliferative response made by the antigen-presenting cells of the parent
B) A very weak response by the child's T cells, involving only 0.1% of their T cells
C) The complete absence of any proliferative response by the child's T cells
D) A robust cytolytic response that kills all of the parent's antigen-presenting cells
E) A robust response by the child's T cells

Accepted Answer

In a mixed lymphocyte reaction, the T cells from individual A will make a robust response to antigen-presenting-cells from individual B, as long as the two individuals express different alleles of MHC molecules. Therefore, when a child’s T cells are used as responder cells and the antigen-presenting cells are from one parent, there is a possibility that the child’s T cells will recognize the differences in the MHC molecules expressed by the parent’s cells, leading to a robust response by the child’s T cells. Hence, the best choice is E - "A robust response by the child's T cells".

Question 7

The mechanism of cross-presentation by dendritic cells is an essential pathway for generating CD8 T cell responses to some intracellular pathogens. If this pathway did not exist, we would be highly susceptible to:
A) Intracellular pathogens that can survive inside macrophage endocytic vesicles
B) Intracellular pathogens that are able to evade antibody responses
C) Intracellular pathogens that do not infect and replicate in dendritic cells
D) Intracellular pathogens that can spread from cell to cell by inducing cell fusion
E) Intracellular pathogens that infect and replicate in red blood cells

Accepted Answer

Cross-presentation by dendritic cells is specifically important for generating CD8 T cell responses to intracellular pathogens that do not infect and replicate in dendritic cells. Therefore, if this pathway did not exist, we would be highly susceptible to such pathogens. Option A is incorrect because macrophages have their own mechanisms for processing and presenting antigens to CD8 T cells. Option B is unrelated to cross-presentation by dendritic cells. Option D and E are also unrelated as they describe different modes of pathogen spread and infectivity.

Question 8

Virus infections induce production of interferons that act on infected cells to enhance their recognition by CD8 cytotoxic T cells. To counter these mechanisms, viruses often encode proteins that interfere with antigen processing and presentation. In an experiment, cells infected with Virus X are treated with interferon and compared with uninfected cells treated with interferon. Proteasomes are isolated from the two cell populations and their enzymatic activities are compared. The data in Figure show the amino acid preferences for cleavage of peptides by the two samples of proteasomes. 
 Based on these data, Virus X most likely encodes a protein that interferes with:
A) The expression of MHC class I on the surface of the infected cell
B) The rate at which peptides are produced from intact proteins in the infected cell
C) The transport of peptides from the cytosol to the endoplasmic reticulum in the infected cell
D) The replacement of constitutive proteasome subunits with immunoproteasome subunits in the infected cell
E) The development of CD8 T cells in the thymus by inhibiting the thymoproteasome

Accepted Answer

The answer of Virus infections induce production of interferons that...

Question 9

The virus shown in the diagram below is only able to infect and replicate in epithelial cells. In order for the cross-presenting dendritic cell to display viral peptides, rather than self peptides on its surface MHC class I proteins, which of the following procedures could be utilized, starting with the components shown in Figure?

A) Mix epithelial cells with heat-killed virus, wait 24 hrs, wash away any virus particles outside the epithelial cells, then add epithelial cells to dendritic cells.
B) Mix epithelial cells with viral peptides, wait 24 hrs, wash away any viral peptides not bound to the epithelial cells, then add epithelial cells to dendritic cells.
C) Mix epithelial cells with live virus particles, wait 24 hrs, wash away any virus particles outside the epithelial cells, then add epithelial cells to dendritic cells.
D) Mix dendritic cells with viral nucleic acids and epithelial cells for 24 hrs.
E) MIx epithelial cells will viral nucleic acids, wait 24 hrs, wash away any viral nucleic acid remaining outside the epithelial cells, then add epithelial cells to dendritic cells.

Accepted Answer

The answer of The virus shown in the diagram below...

Question 10

Some viruses have mechanisms to down-regulate MHC class I protein expression on the surface of cells in which the virus is replicating. This immune evasion strategy might prevent effector CD8 cytotoxic T cells from recognizing and killing the virus-infected cells. Would this immune evasion strategy also prevent the initial activation of virus-specific CD8 T cells?
A) Yes, because no viral peptide:MHC class I complexes would form to activate CD8 T cells.
B) No, because dendritic cells would take up infected cells and cross-present viral peptides to activate CD8 T cells.
C) No, because some presentation of MHC class I complexes with viral peptides would occur before the virus could down-regulate all the surface MHC class I protein.
D) Yes, because this immune evasion strategy would also function in dendritic cells, even if the virus doesn't replicate in dendritic cells.
E) No, because the type I interferon response induced by the virus infection will up-regulate MHC class I expression and override the immune evasion mechanism.

Accepted Answer

B) Dendritic cells can take up antigens from infected cells and present these antigens on their MHC class I molecules through a process called cross-presentation. This allows dendritic cells to activate CD8 T cells even if the virus-infected cells have down-regulated MHC class I expression.

Question 11

The adaptive immune system uses multiple strategies to generate diversity in our ability to mount responses to a wide array of infectious microorganisms. These strategies include the generation of diverse repertoires of B-cell and T-cell antigen receptors, as well as polymorphism of MHC genes. The polymorphism of MHC genes differs from the diversity of lymphocyte antigen receptors in that:
A) It involves DNA rearrangements at multiple gene segments in the MHC locus.
B) It requires different enzymes than the RAG1/RAG2 recombinase required for antigen receptor rearrangements.
C) It results in a diverse repertoire of clonally distributed receptors on dendritic cells, rather than on lymphocytes.
D) It creates diversity between individuals in the population rather than within a single individual.
E) It does not contribute to the transplant rejection responses that occur after organ transplantation between unrelated individuals.

Accepted Answer

Polymorphism of MHC genes creates diversity between individuals in the population rather than within a single individual. This is because MHC genes are inherited in a codominant manner, meaning an individual can inherit different MHC alleles from each parent, resulting in a diverse pool of MHC alleles within a population. This diversity is important for the ability of the immune system to recognize and respond to a wide range of pathogens.

Question 12

The invariant chain protein, Ii, has only one function in MHC class II antigen presentation. This function entails Ii protein occupying the peptide-binding site of each newly synthesized class II protein, thereby preventing nascent MHC class II proteins from binding peptides or misfolded proteins in the endoplasmic reticulum.

Accepted Answer

The invariant chain (Ii) has multiple functions in MHC class II antigen presentation: besides occupying the peptide-binding site to prevent premature peptide binding, it also facilitates the proper folding of MHC class II molecules, their assembly in the endoplasmic reticulum, and their transport to the endosomal/lysosomal compartments where peptide loading occurs.

Question 13

MHC polymorphism at individual MHC genes appears to have been strongly selected by evolutionary pressures. In other words, there appears to be selection for maintaining hundreds to thousands of different alleles of each MHC gene in the population. This notion is based on the observation that nucleotide differences between alleles that lead to amino acid substitutions are more frequent than those that are silent substitutions (i.e., not changing the amino acid sequence of the protein). In addition, the positions within the MHC protein where most of the allelic sequence variation occurs are not randomly distributed, but are concentrated in certain regions of the MHC protein. This latter point indicates:
A) That some nucleotide sequences within the MHC genes are hot-spots for mutation
B) That MHC genes are more susceptible to point mutations than to larger nucleotide deletions
C) That MHC allelic polymorphism has been driven by selection for diversity in peptide binding specificity
D) That MHC genes are more susceptible to all types of mutations than are other genes in the genome
E) That MHC polymorphism has evolved to prevent pathogens that infect non-human primates from infecting humans

Accepted Answer

The concentration of nucleotide differences leading to amino acid substitutions within certain regions of the MHC protein suggest that selection has favored diversity in peptide binding specificity, which is critical for recognizing and responding to a wide range of pathogenic antigens. This selection pressure likely explains why MHC alleles are so diverse and numerous within populations.

Question 14

The diagram in Figure  shows a pathogen (in red) that is present in different cellular compartments of each of the cell types shown. In each case, a specific T cell subset will recognize peptides of that pathogen presented on MHC molecules on the surface of the cell, and will execute its effector function. From the list below, match the appropriate T cell effector response to the cell type and location of the pathogen.  
i. CD4 T cell killing of target cell
ii. CD8 T cell killing of target cell
iii. CD4 T cell activation of target cell's antibody production
iv. CD8 T cell activation of target cell's antibody production
v. CD4 T cell activation of target cell's ability to kill intracellular pathogen
vi. CD8 T cell activation of target cell's ability to kill intracellular pathogen

Accepted Answer

The answer of The diagram in Figure  shows a...

Question 15

The adaptive immune system developed a strategy for monitoring the proteins synthesized in virtually any cell in the body, thereby preventing pathogens from 'hiding out' by adopting an intracellular lifestyle. To accomplish this, the immune system:
A) Co-opted the ubiquitin-proteasome system used by cell for protein turnover
B) Created a novel pathway using the immunoproteasome for generating peptides
C) Created a novel pathway to express foreign proteins on the cell surface
D) Took advantage of proteolytic enzymes present in endocytic vesicles
E) Engineered an immune-specific ubiquitin molecule for tagging foreign proteins

Accepted Answer

The immune system co-opted the ubiquitin-proteasome system, which is used by cells for protein turnover, to process intracellular proteins into peptides that can be presented on MHC class I molecules, allowing the immune system to monitor intracellular proteins.

Question 16

Empty MHC class I and MHC class II molecules are rapidly removed from the cell surface. This process prevents:
A) The accumulation of empty MHC molecules on the cell surface which would interfere with T cells recognizing pathogen-derived peptide:MHC complexes
B) Pathogens from evading the immune response by inducing peptide release from cell surface MHC molecules
C) MHC class I molecules from being internalized into endosomes and binding endosome-derived peptides
D) HLA-DM from trafficking to the cell surface with MHC class II
E) Inappropriate T cell recognition of healthy cells that are not infected, nor have ingested a pathogen

Accepted Answer

The answer of Empty MHC class I and MHC class...

Question 17

During MHC class I synthesis and folding in the endoplasmic reticulum (ER), a process of peptide editing takes place as the newly synthesized MHC class I protein is held in a 'peptide receptive' state by binding to the calreticulin:ERp57:tapasin complex. Peptide editing ensures that the MHC class I molecules that reach the cell surface have stable, high affinity binding for their peptide cargo. Peptide editing is important to the immune response because it:
A) Maintains high levels of surface MHC class I expression
B) Ensures that MHC class I molecules are not degraded in the ER
C) Retains the nascent MHC class I molecule in a peptide receptive state
D) Allows surface MHC class I molecules to bind new peptides from the extracellular milieu
E) Prevents surface MHC class I molecules from undergoing peptide exchange at the cell surface

Accepted Answer

The answer of During MHC class I synthesis and folding...

Question 18

A cell line carrying a mutation in a single gene is found to express very low levels of MHC class I on its surface. When infected with influenza virus, these cells are not recognized nor are they killed by a CD8 T cell line specific for an influenza peptide bound to the MHC class I protein expressed by these cells. Incubation of the mutant cell line with a large excess of this peptide in the cell culture medium overnight leads to the results shown in 
What is the most likely candidate for the gene that is defective in the mutant cell line?

Accepted Answer

The answer of A cell line carrying a mutation in...

Question 19

Peptide editing is an important component of antigen presentation for both MHC class I and MHC class II pathways, as it drives the preferential presentation of high-affinity binding peptides. For MHC class II peptide editing, HLA-DM plays a key role. In the absence of HLA-DM:
A) MHC class II molecules traffic to the cell surface with CLIP in their binding sites.
B) No MHC class II molecules are released to traffic to the cell surface.
C) MHC class II molecules bind to HLA-DO and are inhibited from binding peptides.
D) Pathogens can evade the immune system by blocking peptide exchange on MHC class II.
E) HLA-DO competes for high-affinity binding peptides with MHC class II molecules and blocks antigen presentation.

Accepted Answer

In the absence of HLA-DM, MHC class II molecules often traffic to the cell surface with CLIP (Class II-associated invariant chain peptide) still bound in their peptide-binding groove, because HLA-DM facilitates the release of CLIP and the binding of other peptides.

Question 20

The genes encoding MHC proteins are closely linked with genes encoding proteins involved in antigen processing and presentation. This genetic linkage facilitates the coordinate regulation of these genes by interferons.

Accepted Answer

The statement is true. The MHC genes and antigen processing/presentation genes are closely linked on the same chromosome and are coordinately regulated by interferons.

Quiz 6: Antigen Presentation to T Lymphocytes

MHC class I surface expression is dependent on an abundant source of pathogen-derived peptides. Thus, in uninfected cells, nearly all of the MHC class I proteins are degraded and never reach the cell surface.

Multiple mechanisms contribute to create a wide diversity in MHC protein expression between different individuals in the population. In addition to the genetic polymorphism of MHC genes, what additional mechanism(s) contribute to this diversity?

The MARCH-1 E3-ubiquitin ligase is expressed in B cells, dendritic cells, and macrophages. The pathway regulated by MARCH-1 is targeted by some pathogens in an immune evasion strategy. In this strategy, the pathogens encode:

The mechanism of cross-presentation by dendritic cells is an essential pathway for generating CD8 T cell responses to some intracellular pathogens. If this pathway did not exist, we would be highly susceptible to:

The adaptive immune system developed a strategy for monitoring the proteins synthesized in virtually any cell in the body, thereby preventing pathogens from 'hiding out' by adopting an intracellular lifestyle. To accomplish this, the immune system:

Empty MHC class I and MHC class II molecules are rapidly removed from the cell surface. This process prevents:

Peptide editing is an important component of antigen presentation for both MHC class I and MHC class II pathways, as it drives the preferential presentation of high-affinity binding peptides. For MHC class II peptide editing, HLA-DM plays a key role. In the absence of HLA-DM:

The genes encoding MHC proteins are closely linked with genes encoding proteins involved in antigen processing and presentation. This genetic linkage facilitates the coordinate regulation of these genes by interferons.