Podcast
Questions and Answers
Which cell types can express HLA-2?
Which cell types can express HLA-2?
- Erythrocytes and platelets
- Smooth muscle cells and fibroblasts
- Macrophages and dendritic cells (correct)
- Neurons and astrocytes
Which type of antigen (intracellular or extracellular) corresponds to HLA-1 presentation?
Which type of antigen (intracellular or extracellular) corresponds to HLA-1 presentation?
- Intracellular (correct)
- Extracellular
- Both intracellular and extracellular
- None of the above
What is the process by which exogenous antigens can be presented by HLA-1?
What is the process by which exogenous antigens can be presented by HLA-1?
- Cross-migration
- Autophagy leading to presentation on HLA-2
- Antigens leaking out of endosomes into the cytosol (correct)
- Phagocytosis into the cytosol
What is the function of cross-presentation in antigen presenting cells?
What is the function of cross-presentation in antigen presenting cells?
After a peptide-bound HLA-2 is expressed on the cell surface, what happens next?
After a peptide-bound HLA-2 is expressed on the cell surface, what happens next?
What is the primary role of dendritic cells in cross-presentation?
What is the primary role of dendritic cells in cross-presentation?
What is the major CD that distinguishes a Helper T-cell from a cytotoxic T-cell?
What is the major CD that distinguishes a Helper T-cell from a cytotoxic T-cell?
What is the co-receptor for a cytotoxic T cell?
What is the co-receptor for a cytotoxic T cell?
Which molecule interacts with CD28 on T-cells for co-stimulatory activation?
Which molecule interacts with CD28 on T-cells for co-stimulatory activation?
Which cells have the capacity to up-regulate CD80/86 after they are activated by an encounter with a pathogen?
Which cells have the capacity to up-regulate CD80/86 after they are activated by an encounter with a pathogen?
Which type of HLA is involved in the endogenous antigen presentation pathway?
Which type of HLA is involved in the endogenous antigen presentation pathway?
When is the antigen loaded onto the HLA protein in the exogenous antigen presentation pathway?
When is the antigen loaded onto the HLA protein in the exogenous antigen presentation pathway?
How are cytotoxic T cells activated?
How are cytotoxic T cells activated?
What types of cells might present the HLA bound antigen in the endogenous antigen presentation pathway?
What types of cells might present the HLA bound antigen in the endogenous antigen presentation pathway?
What distinguishes foreign antigens from self antigens for T-cells?
What distinguishes foreign antigens from self antigens for T-cells?
Why can HLA proteins present a wide variety of antigens to a wide variety of lymphocytes?
Why can HLA proteins present a wide variety of antigens to a wide variety of lymphocytes?
How is an HLA class II molecule loaded with antigen?
How is an HLA class II molecule loaded with antigen?
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 ensures that a cytosolic antigen isn’t loaded onto an HLA-2 in the rough endoplasmic reticulum?
What ensures that a cytosolic antigen isn’t loaded onto an HLA-2 in the rough endoplasmic reticulum?
In the endogenous pathway of HLA-1 expression, where is the source of the antigenic peptide?
In the endogenous pathway of HLA-1 expression, where is the source of the antigenic peptide?
What is responsible for loading the antigenic peptide onto the HLA-1 protein in the endogenous pathway?
What is responsible for loading the antigenic peptide onto the HLA-1 protein in the endogenous pathway?
What happens to the loaded HLA-1 in the endogenous pathway?
What happens to the loaded HLA-1 in the endogenous pathway?
What is the source of the antigenic peptide in the exogenous pathway of HLA-2 expression?
What is the source of the antigenic peptide in the exogenous pathway of HLA-2 expression?
Where are HLA-2 bound peptides transported to in the exogenous pathway?
Where are HLA-2 bound peptides transported to in the exogenous pathway?
What happens to the loaded HLA-2 in the exogenous pathway?
What happens to the loaded HLA-2 in the exogenous pathway?
What is the main difference between antigens in endogenous and exogenous pathways?
What is the main difference between antigens in endogenous and exogenous pathways?
Where is the does the antigen bind on an HLA-1 molecule?
Where is the does the antigen bind on an HLA-1 molecule?
CD8 binds to the alpha-3 subunit of HLA_1
CD8 binds to the alpha-3 subunit of HLA_1
Where is the does the antigen bind on an HLA-2 molecule?
Where is the does the antigen bind on an HLA-2 molecule?
Which of the following cells always express high levels of HLA-2?
Which of the following cells always express high levels of HLA-2?
B-cells always express HLA-2 at low levels
B-cells always express HLA-2 at low levels
___________ needs to be up-regulated in concurrence with HLA-2 expression (think of a process not a molecule)
___________ needs to be up-regulated in concurrence with HLA-2 expression (think of a process not a molecule)
Which of the following will prevent an exogenous antigen from loading onto an HLA-1?
Which of the following will prevent an exogenous antigen from loading onto an HLA-1?
The chopped version of the invariant chain is known as _______
The chopped version of the invariant chain is known as _______
Dendritic cells are the only APC that always express CD80/86
Dendritic cells are the only APC that always express CD80/86
cSMAC includes the binding between TCR and an HLA only
cSMAC includes the binding between TCR and an HLA only
What is the effect of paracrine signaling between APC and T-cells?
What is the effect of paracrine signaling between APC and T-cells?
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Study Notes
HLA Expression and Antigen Presentation
- HLA-2 can be expressed by antigen presenting cells, including dendritic cells, macrophages, and B cells.
- HLA-1 presents extracellular antigens, which are typically derived from outside the cell.
- Exogenous antigens are presented by HLA-1 through a process called cross-presentation, where antigen presenting cells can take up extracellular antigens and present them to CD8+ cytotoxic T cells.
Antigen Presentation Process
- After a peptide binds to HLA-2 and is expressed on the cell surface, it engages T cells, initiating an immune response.
- Dendritic cells play a crucial role in cross-presentation by capturing antigens from outside and presenting them in a way that activates both CD4+ helper and CD8+ cytotoxic T cells.
- Helper T cells can be distinguished from cytotoxic T cells by the expression of CD4.
- The co-receptor for cytotoxic T cells is CD8.
Co-Stimulatory Activation
- CD28 on T cells interacts with CD80/CD86 on antigen presenting cells for necessary co-stimulatory signals.
- Antigen presenting cells can up-regulate CD80/CD86 in response to pathogen encounters.
Antigen Presentation Pathways
- HLA class I is involved in the endogenous antigen presentation pathway.
- In the exogenous pathway, antigens are loaded onto HLA class II molecules after being processed and transported into the endosomal/lysosomal compartments.
- Cytotoxic T cells require antigen presentation via HLA-1 for activation and recognition of infected cells.
Antigen Sources and Recognition
- Endogenous pathway utilizes intracellular sources for antigenic peptides, typically from proteins synthesized within the cell.
- Exogenous pathway utilizes processed antigens derived from the external environment.
- T cells differentiate self antigens from foreign antigens through specific recognition by their receptors; self-antigens are usually presented by HLA without activating T cells.
HLA and Antigen Binding
- HLA proteins can present a diverse range of antigens due to their polymorphic nature and ability to bind various peptide sequences.
- Antigens bind to the α1 and α2 subunits of HLA-1, while HLA-2 accommodates antigen binding to the β1 and α1 subunits.
Special Notes on HLA and Co-Expression
- B cells consistently express low levels of HLA-2, which can be up-regulated upon activation.
- A fragment of the invariant chain prevents exogenous antigens from loading onto HLA-1.
- Dendritic cells uniquely express high levels of CD80/CD86, essential for effective T cell activation.
cSMAC and Signaling
- cSMAC, or central supramolecular activation cluster, involves binding between T cell receptors (TCR) and HLA molecules, fostering signal transduction during immune responses.
- Paracrine signaling between antigen presenting cells and T cells enhances T cell proliferation and activation, leading to a robust immune response.
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