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Questions and Answers
What is implied about the binding of antigens to proteins based on the text?
What is implied about the binding of antigens to proteins based on the text?
- Antigens are bound tightly to proteins.
- Antigens are only bound to HLA class I proteins.
- Antigens are not bound tightly to proteins. (correct)
- Antigens are only bound to HLA class II proteins.
What is a characteristic of MHC-like proteins?
What is a characteristic of MHC-like proteins?
- They only present antigens to lymphocytes.
- They have a wide range of functions beyond presenting antigens. (correct)
- They are only found on the surface of cytotoxic T-cells.
- They have a limited range of functions.
What is a key difference between HLA class I and HLA class II proteins?
What is a key difference between HLA class I and HLA class II proteins?
- HLA class I presents extracellular antigens, while HLA class II presents intracellular antigens.
- HLA class I interacts with cytotoxic T-cells, while HLA class II interacts with T-helper cells. (correct)
- HLA class I interacts with T-helper cells, while HLA class II interacts with cytotoxic T-cells.
- HLA class I presents antigens 5-7 amino acids long, while HLA class II presents antigens 8-10 amino acids long.
What is the function of the CD8 co-receptor on cytotoxic T-cells?
What is the function of the CD8 co-receptor on cytotoxic T-cells?
What is the role of the β2 microglobulin subunit in HLA class I proteins?
What is the role of the β2 microglobulin subunit in HLA class I proteins?
What is the length of antigens bound by HLA-I?
What is the length of antigens bound by HLA-I?
Which type of cells exclusively express HLA-2?
Which type of cells exclusively express HLA-2?
Which of the following antigen presenting cells constitutively express high levels of HLA-2?
Which of the following antigen presenting cells constitutively express high levels of HLA-2?
Which type of antigen presenting cells need to be activated before they express HLA-2?
Which type of antigen presenting cells need to be activated before they express HLA-2?
What is a characteristic of non-professional antigen presenting cells in terms of HLA-2 expression?
What is a characteristic of non-professional antigen presenting cells in terms of HLA-2 expression?
What is the function of HLA-2 in antigen presenting cells?
What is the function of HLA-2 in antigen presenting cells?
Which of the following is NOT a type of professional antigen presenting cell?
Which of the following is NOT a type of professional antigen presenting cell?
What is the primary source of the antigenic peptide in the endogenous pathway?
What is the primary source of the antigenic peptide in the endogenous pathway?
What is the primary function of immunoproteosomes in antigen processing?
What is the primary function of immunoproteosomes in antigen processing?
What happens to the peptide after it is derived from proteasomal degradation?
What happens to the peptide after it is derived from proteasomal degradation?
What is the primary function of HLA-1 proteins?
What is the primary function of HLA-1 proteins?
What is the difference between HLA-1 molecules expressed during viral infection and those expressed during normal conditions?
What is the difference between HLA-1 molecules expressed during viral infection and those expressed during normal conditions?
What is the result of the endogenous pathway of antigen processing?
What is the result of the endogenous pathway of antigen processing?
What is the purpose of proteasomal degradation in antigen processing?
What is the purpose of proteasomal degradation in antigen processing?
What is the significance of HLA-1 molecules expressing self-antigens?
What is the significance of HLA-1 molecules expressing self-antigens?
What is necessary for HLA-2 proteins to bind extracellular antigens via the exogenous pathway?
What is necessary for HLA-2 proteins to bind extracellular antigens via the exogenous pathway?
Which cytokine is particularly good at up-regulating HLA-2 expression?
Which cytokine is particularly good at up-regulating HLA-2 expression?
What is the role of phagocytosis in the exogenous pathway?
What is the role of phagocytosis in the exogenous pathway?
What is the role of HLA-DM in antigen processing?
What is the role of HLA-DM in antigen processing?
In which cells does IL-4 up-regulate HLA-2 expression?
In which cells does IL-4 up-regulate HLA-2 expression?
What is the result of phagocytosis in the exogenous pathway?
What is the result of phagocytosis in the exogenous pathway?
Where are HLA class I molecules typically found?
Where are HLA class I molecules typically found?
Under what circumstances can exogenous antigens be presented by HLA class I molecules?
Under what circumstances can exogenous antigens be presented by HLA class I molecules?
What is the fate of the antibody after receptor-mediated endocytosis in B-cells?
What is the fate of the antibody after receptor-mediated endocytosis in B-cells?
What happens to viral particles in the cytosol of an infected cell that is phagocytosed?
What happens to viral particles in the cytosol of an infected cell that is phagocytosed?
How do HLA class I and HLA class II molecules differ in terms of antigen processing?
How do HLA class I and HLA class II molecules differ in terms of antigen processing?
What is the role of HLA-2 proteins in the exogenous pathway?
What is the role of HLA-2 proteins in the exogenous pathway?
What is necessary for HLA-2 proteins to express antigens on the surface of the cell?
What is necessary for HLA-2 proteins to express antigens on the surface of the cell?
What determines whether antigenic peptides associate with HLA class I or HLA class II molecules?
What determines whether antigenic peptides associate with HLA class I or HLA class II molecules?
Where are HLA class II molecules typically found?
Where are HLA class II molecules typically found?
What is the result of interferon-gamma on HLA-2 expression in B-cells?
What is the result of interferon-gamma on HLA-2 expression in B-cells?
What is the role of HLA-DO in antigen processing?
What is the role of HLA-DO in antigen processing?
What is the function of the invariant chain in the RER?
What is the function of the invariant chain in the RER?
What happens to the invariant chain when the HLA-2 containing vesicle merges with the phagosome/endosome?
What happens to the invariant chain when the HLA-2 containing vesicle merges with the phagosome/endosome?
What is required for a peptide to bind to HLA-2 proteins?
What is required for a peptide to bind to HLA-2 proteins?
What is the final step in the exogenous pathway of antigen processing?
What is the final step in the exogenous pathway of antigen processing?
What is the purpose of CLIP in the exogenous pathway?
What is the purpose of CLIP in the exogenous pathway?
In which compartment do HLA-2 proteins associate with the invariant chain?
In which compartment do HLA-2 proteins associate with the invariant chain?
What is the fate of CLIP after a peptide binds to HLA-2 proteins?
What is the fate of CLIP after a peptide binds to HLA-2 proteins?
What is the role of the invariant chain in preventing the loading of cytosolic antigens onto HLA-2 proteins?
What is the role of the invariant chain in preventing the loading of cytosolic antigens onto HLA-2 proteins?
What is the primary function of HLA proteins in antigen presentation?
What is the primary function of HLA proteins in antigen presentation?
Which type of cells can present antigens using HLA proteins?
Which type of cells can present antigens using HLA proteins?
What is the key difference between HLA-1 and HLA-2 proteins?
What is the key difference between HLA-1 and HLA-2 proteins?
What is the purpose of antigen presentation in T-cell activation?
What is the purpose of antigen presentation in T-cell activation?
What is cross-presentation, and which cells can perform it?
What is cross-presentation, and which cells can perform it?
What is the role of HLA proteins in distinguishing between foreign and self antigens?
What is the role of HLA proteins in distinguishing between foreign and self antigens?
What is the result of antigen presentation in T-cell activation?
What is the result of antigen presentation in T-cell activation?
Which of the following is a characteristic of HLA proteins?
Which of the following is a characteristic of HLA proteins?
What is the function of HLA-DM in antigen processing?
What is the function of HLA-DM in antigen processing?
What is the primary function of HLA-1 molecules on the surface of a cell?
What is the primary function of HLA-1 molecules on the surface of a cell?
Where do antigens processed in the exogenous pathway associate with?
Where do antigens processed in the exogenous pathway associate with?
Under what circumstances can exogenous antigens be presented by HLA class I molecules?
Under what circumstances can exogenous antigens be presented by HLA class I molecules?
Which type of cytokines can increase the expression of HLA-1 molecules?
Which type of cytokines can increase the expression of HLA-1 molecules?
What happens to viral particles in the cytosol of an infected cell that is phagocytosed?
What happens to viral particles in the cytosol of an infected cell that is phagocytosed?
What is the source of cytokines that increase HLA-1 expression?
What is the source of cytokines that increase HLA-1 expression?
What determines whether antigenic peptides associate with HLA class I or HLA class II molecules?
What determines whether antigenic peptides associate with HLA class I or HLA class II molecules?
What is the function of activated cytotoxic T-cells?
What is the function of activated cytotoxic T-cells?
What is the role of HLA-DO in antigen processing?
What is the role of HLA-DO in antigen processing?
What type of pathway is involved in the presentation of antigens by HLA-1 molecules?
What type of pathway is involved in the presentation of antigens by HLA-1 molecules?
What is the source of interferon-gamma in the context of HLA-1 expression?
What is the source of interferon-gamma in the context of HLA-1 expression?
What is the significance of HLA-2 molecules in antigen processing?
What is the significance of HLA-2 molecules in antigen processing?
What is the result of phagocytosis in the exogenous pathway?
What is the result of phagocytosis in the exogenous pathway?
What is the primary function of immunoproteosomes in antigen processing?
What is the primary function of immunoproteosomes in antigen processing?
Which cytokines can induce the substitution of different subunits into the regular proteosome?
Which cytokines can induce the substitution of different subunits into the regular proteosome?
What is the role of TAP in antigen processing?
What is the role of TAP in antigen processing?
What is the result of immunoproteosomes substituting different subunits into the regular proteosome?
What is the result of immunoproteosomes substituting different subunits into the regular proteosome?
Why are some viruses able to block the expression of their viral peptides on the surface of infected cells?
Why are some viruses able to block the expression of their viral peptides on the surface of infected cells?
What is necessary for the loading of peptides onto HLA-1?
What is necessary for the loading of peptides onto HLA-1?
What is the result of the endogenous pathway of antigen processing?
What is the result of the endogenous pathway of antigen processing?
Which type of cells express HLA-1?
Which type of cells express HLA-1?
Study Notes
HLA Proteins
- HLA proteins are not bound tightly to antigens, allowing them to present a wide variety of antigens to a wide variety of lymphocytes.
- There are also a wide variety of genes/proteins called "MHC-like" that have a range of functions beyond simply presenting antigens.
HLA Class I and II Proteins
- HLA Class I proteins:
- Interact with cytotoxic T-cells and bind intracellular antigens.
- Interact with a CD8 co-receptor on the cytotoxic T-cell.
- HLA Class II proteins:
- Interact with T-helper cells and bind extracellular antigens.
- Interact with a CD4 co-receptor on the T-helper cell.
HLA-I Structure
- The antigen binding site is found between the α1 and α2 subunits of the glycoprotein heavy chain.
- The CD8 co-receptor on the cytotoxic T-cell binds to the α3 subunit.
- β2 microglobulin subunit is not covalently bound to the heavy chain and is needed for proper folding.
HLA-1 Expression and Function
- HLA-1 proteins bind intracellular antigens via the endogenous pathway.
- Most of the time, these are self-antigens, but in the case of infection or malignancy, the peptide can be foreign.
- During viral infection, some HLA-1 molecules on a cell will express viral peptides, while some will express host peptides.
HLA-1 Expression: Endogenous Pathway
- Antigen processing:
- Source of the antigenic peptide is from the cytosol.
- The peptide is derived from proteasomal degradation of foreign/altered proteins (or normal self-antigens).
- The peptide is then transported into the RER and loaded onto the HLA-1 protein.
- The loaded HLA-1 is then expressed on the cell surface.
HLA-2 Expression and Function
- HLA-2 types are expressed exclusively on antigen presenting cells (APCs).
- APCs include:
- Dendritic cells
- Macrophages
- B-cells
- Non-professional APCs (e.g. fibroblasts, glial cells, pancreatic beta cells, thymic epithelial cells, intraepithelial lymphocytes, vascular endothelial cells)
- However, some of these APCs won't even express HLA-2 unless they've been activated.
HLA-2 Expression: Exogenous Pathway
- HLA-2 proteins bind extracellular antigens via the exogenous pathway.
- Phagocytosis needs to be upregulated in concurrence with HLA-2 expression.
- Phagocytosis is the source of the peptides that are loaded onto the HLA-2.
- Phagocytosis can occur through the "regular" pathway or antibody-mediated in the case of B-cells.
Antigen Processing Exceptions
- Exogenous antigens can be presented by HLA-1, and endogenous antigens can be presented by HLA-2 in some circumstances.
- For example, an infected cell dies and is phagocytosed, and viral particles in the cytosol of the infected cell will be presented on HLA-2 of the phagocyte.
HLA-2 Expression: Exogenous Pathway
- HLA-2 proteins bind extracellular antigens via the exogenous pathway.
- In the RER, HLA-2 protein associates with the invariant chain (CD74) to prevent cytosolic antigens from being loaded onto HLA-2.
- As the HLA-2 containing vesicle merges with the phagosome/endosome containing the antigen, the invariant chain is chopped up into a "chopped version" called CLIP.
- CLIP remains bound to the HLA-2 peptide binding region until displaced by a peptide with sufficient affinity to HLA-2.
- When a peptide binds with sufficient affinity to HLA-2, CLIP is displaced, and HLA-2 with bound extracellular antigen is expressed on the surface of the cell.
Overview of Antigen Presentation
- Antigen presentation is necessary for T-cell activation.
- HLA proteins present antigens to T-cells in a specific fashion.
- Antigens must be presented to a T-cell in order for them to recognize the antigen.
- HLA proteins help a T-cell distinguish between foreign and self-antigens.
T-Cells and Antigen – Necessity of HLA
- A wide variety of cells can present antigens using HLA proteins.
- HLA proteins are bound to antigens, but are not genetically "shuffled" like lymphocyte receptors.
HLA-1 Expression: Endogenous Pathway
- Antigen processing occurs via the endogenous pathway.
- The protein that translocates the peptide fragment into the RER for loading onto HLA-1 is called TAP.
- Cytokines can increase the expression of HLA-1 molecules.
- Tumour necrosis factor alpha (TNFα) and type 1 interferons (IFN) can increase HLA-1 expression.
HLA-1 – What Happens Next
- Once a peptide-bound HLA-1 is expressed on the surface of a cell, it can bind to a CD8+ T-cell and activate it.
- Activated cytotoxic T-cells can kill infected cells by inducing apoptosis.
HLA Types Summary
- HLA-1: presents intracellular antigens to CD8+ T-cells via the endogenous pathway.
- HLA-2: presents extracellular antigens to CD4+ T-cells via the exogenous pathway.
Antigen-Processing Exceptions
- Exogenous antigens can be presented by HLA-1, and endogenous antigens can be presented by HLA-2 in some circumstances, such as cross-presentation.
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Description
Learn about the role of HLA proteins in presenting antigens to lymphocytes, their types, and functions. Understand HLA class I and II proteins and their interactions with immune cells.
