HLA Proteins and Antigen Presentation

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Questions and Answers

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?

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?

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?

It binds to the ⍺3 subunit of HLA class I proteins. Signup and view all the answers

What is the role of the β2 microglobulin subunit in HLA class I proteins?

It is not covalently bound to the heavy chain and is necessary for proper folding. Signup and view all the answers

What is the length of antigens bound by HLA-I?

8-10 amino acids long Signup and view all the answers

Which type of cells exclusively express HLA-2?

Antigen presenting cells Signup and view all the answers

Which of the following antigen presenting cells constitutively express high levels of HLA-2?

Dendritic cells Signup and view all the answers

Which type of antigen presenting cells need to be activated before they express HLA-2?

Macrophages Signup and view all the answers

What is a characteristic of non-professional antigen presenting cells in terms of HLA-2 expression?

They only express HLA-2 under particular conditions Signup and view all the answers

What is the function of HLA-2 in antigen presenting cells?

To co-stimulate helper-T-cells Signup and view all the answers

Which of the following is NOT a type of professional antigen presenting cell?

Fibroblasts Signup and view all the answers

What is the primary source of the antigenic peptide in the endogenous pathway?

The cytosol Signup and view all the answers

What is the primary function of immunoproteosomes in antigen processing?

To present peptides to T-cells Signup and view all the answers

What happens to the peptide after it is derived from proteasomal degradation?

It is transported into the RER and loaded onto the HLA-1 protein Signup and view all the answers

What is the primary function of HLA-1 proteins?

To bind intracellular antigens via the endogenous pathway Signup and view all the answers

What is the difference between HLA-1 molecules expressed during viral infection and those expressed during normal conditions?

Some HLA-1 molecules express viral peptides, while others express host peptides Signup and view all the answers

What is the result of the endogenous pathway of antigen processing?

The loaded HLA-1 is then expressed on the cell surface Signup and view all the answers

What is the purpose of proteasomal degradation in antigen processing?

To derive antigenic peptides from foreign/altered proteins or normal self-antigens Signup and view all the answers

What is the significance of HLA-1 molecules expressing self-antigens?

It inhibits an immune response against the self-antigens Signup and view all the answers

What is necessary for HLA-2 proteins to bind extracellular antigens via the exogenous pathway?

Up-regulation of phagocytosis Signup and view all the answers

Which cytokine is particularly good at up-regulating HLA-2 expression?

Interferon-gamma Signup and view all the answers

What is the role of phagocytosis in the exogenous pathway?

To provide peptides for loading onto HLA-2 Signup and view all the answers

What is the role of HLA-DM in antigen processing?

It helps with loading of antigens onto HLA-2 Signup and view all the answers

In which cells does IL-4 up-regulate HLA-2 expression?

B-cells Signup and view all the answers

What is the result of phagocytosis in the exogenous pathway?

Antigen is loaded onto HLA-2 Signup and view all the answers

Where are HLA class I molecules typically found?

In the endoplasmic reticulum Signup and view all the answers

Under what circumstances can exogenous antigens be presented by HLA class I molecules?

During cross-presentation Signup and view all the answers

What is the fate of the antibody after receptor-mediated endocytosis in B-cells?

It is recycled back to the surface of the cell Signup and view all the answers

What happens to viral particles in the cytosol of an infected cell that is phagocytosed?

They are presented on HLA class II molecules of the phagocyte Signup and view all the answers

How do HLA class I and HLA class II molecules differ in terms of antigen processing?

HLA class I molecules process antigens from the cytosol, while HLA class II molecules process antigens from the extracellular environment Signup and view all the answers

What is the role of HLA-2 proteins in the exogenous pathway?

To bind extracellular antigens Signup and view all the answers

What is necessary for HLA-2 proteins to express antigens on the surface of the cell?

Loading of peptides onto HLA-2 Signup and view all the answers

What determines whether antigenic peptides associate with HLA class I or HLA class II molecules?

The mode of antigen entry into cells and the site of antigen processing Signup and view all the answers

Where are HLA class II molecules typically found?

In endocytic compartments Signup and view all the answers

What is the result of interferon-gamma on HLA-2 expression in B-cells?

Down-regulation of HLA-2 Signup and view all the answers

What is the role of HLA-DO in antigen processing?

It inhibits the loading of antigens onto HLA-2 Signup and view all the answers

What is the function of the invariant chain in the RER?

To prevent cytosolic antigens from being loaded onto HLA-2 proteins Signup and view all the answers

What happens to the invariant chain when the HLA-2 containing vesicle merges with the phagosome/endosome?

It is chopped up into CLIP Signup and view all the answers

What is required for a peptide to bind to HLA-2 proteins?

High affinity and displacement of CLIP Signup and view all the answers

What is the final step in the exogenous pathway of antigen processing?

Expression of HLA-2 proteins on the cell surface Signup and view all the answers

What is the purpose of CLIP in the exogenous pathway?

To prevent the binding of peptides to HLA-2 proteins Signup and view all the answers

In which compartment do HLA-2 proteins associate with the invariant chain?

RER Signup and view all the answers

What is the fate of CLIP after a peptide binds to HLA-2 proteins?

It is displaced Signup and view all the answers

What is the role of the invariant chain in preventing the loading of cytosolic antigens onto HLA-2 proteins?

It binds to HLA-2 proteins and prevents antigen loading Signup and view all the answers

What is the primary function of HLA proteins in antigen presentation?

To facilitate the interaction between T-cells and antigens Signup and view all the answers

Which type of cells can present antigens using HLA proteins?

A wide variety of cells Signup and view all the answers

What is the key difference between HLA-1 and HLA-2 proteins?

HLA-1 binds to endogenous antigens, while HLA-2 binds to exogenous antigens Signup and view all the answers

What is the purpose of antigen presentation in T-cell activation?

To activate T-cells against foreign antigens Signup and view all the answers

What is cross-presentation, and which cells can perform it?

The presentation of exogenous antigens to T-cells, and dendritic cells and macrophages can perform it Signup and view all the answers

What is the role of HLA proteins in distinguishing between foreign and self antigens?

To help T-cells distinguish between foreign and self antigens Signup and view all the answers

What is the result of antigen presentation in T-cell activation?

T-cell activation Signup and view all the answers

Which of the following is a characteristic of HLA proteins?

They are not genetically shuffled like lymphocyte receptors Signup and view all the answers

What is the function of HLA-DM in antigen processing?

To help with the loading of antigens onto HLA-2 Signup and view all the answers

What is the primary function of HLA-1 molecules on the surface of a cell?

To bind a CD8+ T-cells Cytotoxic T cell and activate it Signup and view all the answers

Where do antigens processed in the exogenous pathway associate with?

HLA class II molecules in endocytic compartments Signup and view all the answers

Under what circumstances can exogenous antigens be presented by HLA class I molecules?

During cross-presentation Signup and view all the answers

Which type of cytokines can increase the expression of HLA-1 molecules?

Type 1 and type 2 interferons, and tumour necrosis factor alpha Signup and view all the answers

What happens to viral particles in the cytosol of an infected cell that is phagocytosed?

They are presented on HLA-2 molecules Signup and view all the answers

What is the source of cytokines that increase HLA-1 expression?

Local antigen-presenting cells and later activated T-helper cells Signup and view all the answers

What determines whether antigenic peptides associate with HLA class I or HLA class II molecules?

The mode of antigen entry into cells and the site of antigen processing Signup and view all the answers

What is the function of activated cytotoxic T-cells?

To kill infected cells by inducing apoptosis Signup and view all the answers

What is the role of HLA-DO in antigen processing?

To inhibit the loading of antigens onto HLA-2 Signup and view all the answers

What type of pathway is involved in the presentation of antigens by HLA-1 molecules?

Endogenous pathway Signup and view all the answers

What is the source of interferon-gamma in the context of HLA-1 expression?

Activated T-helper cells Signup and view all the answers

What is the significance of HLA-2 molecules in antigen processing?

They present antigens to CD4+ T-cells Signup and view all the answers

What is the result of phagocytosis in the exogenous pathway?

Antigens are presented on HLA-2 molecules Signup and view all the answers

What is the primary function of immunoproteosomes in antigen processing?

To substitute different subunits into the regular proteosome Signup and view all the answers

Which cytokines can induce the substitution of different subunits into the regular proteosome?

IFN-gamma and TNF-alpha Signup and view all the answers

What is the role of TAP in antigen processing?

To translocate the peptide fragment into the RER for loading onto HLA-1 Signup and view all the answers

What is the result of immunoproteosomes substituting different subunits into the regular proteosome?

The production of peptides that bind with high affinity to HLA-1 Signup and view all the answers

Why are some viruses able to block the expression of their viral peptides on the surface of infected cells?

Because they can block TAP Signup and view all the answers

What is necessary for the loading of peptides onto HLA-1?

The presence of ATP Signup and view all the answers

What is the result of the endogenous pathway of antigen processing?

The presentation of antigens to T-cells Signup and view all the answers

Which type of cells express HLA-1?

All cells, as part of the endogenous pathway Signup and view all the answers

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.