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Questions and Answers
Which cell types can express HLA-2?
Which type of antigen (intracellular or extracellular) corresponds to HLA-1 presentation?
What is the process by which exogenous antigens can be presented by HLA-1?
What is the function of cross-presentation in antigen presenting cells?
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After a peptide-bound HLA-2 is expressed on the cell surface, what happens next?
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What is the primary role of dendritic cells in cross-presentation?
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What is the major CD that distinguishes a Helper T-cell from a cytotoxic T-cell?
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What is the co-receptor for a cytotoxic T cell?
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Which molecule interacts with CD28 on T-cells for co-stimulatory activation?
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Which cells have the capacity to up-regulate CD80/86 after they are activated by an encounter with a pathogen?
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Which type of HLA is involved in the endogenous antigen presentation pathway?
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When is the antigen loaded onto the HLA protein in the exogenous antigen presentation pathway?
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How are cytotoxic T cells activated?
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What types of cells might present the HLA bound antigen in the endogenous antigen presentation pathway?
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What distinguishes foreign antigens from self antigens for T-cells?
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Why can HLA proteins present a wide variety of antigens to a wide variety of lymphocytes?
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How is an HLA class II molecule loaded with antigen?
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Under what circumstances can exogenous antigens be presented by HLA class I molecules?
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What ensures that a cytosolic antigen isn’t loaded onto an HLA-2 in the rough endoplasmic reticulum?
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In the endogenous pathway of HLA-1 expression, where is the source of the antigenic peptide?
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What is responsible for loading the antigenic peptide onto the HLA-1 protein in the endogenous pathway?
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What happens to the loaded HLA-1 in the endogenous pathway?
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What is the source of the antigenic peptide in the exogenous pathway of HLA-2 expression?
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Where are HLA-2 bound peptides transported to in the exogenous pathway?
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What happens to the loaded HLA-2 in the exogenous pathway?
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What is the main difference between antigens in endogenous and exogenous pathways?
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Where is the does the antigen bind on an HLA-1 molecule?
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CD8 binds to the alpha-3 subunit of HLA_1
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Where is the does the antigen bind on an HLA-2 molecule?
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Which of the following cells always express high levels of HLA-2?
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B-cells always express HLA-2 at low levels
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___________ needs to be up-regulated in concurrence with HLA-2 expression (think of a process not a molecule)
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Which of the following will prevent an exogenous antigen from loading onto an HLA-1?
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The chopped version of the invariant chain is known as _______
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Dendritic cells are the only APC that always express CD80/86
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cSMAC includes the binding between TCR and an HLA only
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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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Description
Test your understanding of T-cell activation and co-receptors with this quiz. Explore the roles of antigen presenting cells, T-cell receptors, HLA-2 molecules, and CD4 co-receptors in the immune response.