Term
| What does it mean for a cell to be capable of "cross presentation"? |
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Definition
| Antigen-presenting cells that can take up, process and present extracellular antigens with MHC class I molecules to CD T cells (cytotoxic T cells) |
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Term
| How can T-cells be "primed" by antigen presenting cells? |
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Definition
| Co-stimulation (signal 2) with combination of surface molecules and cytokines |
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Term
| Explain the process of MHC restriction in T-cell mediated antigen recognition. |
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Definition
T-lymphocytes recognize peptide (can also sometimes be lipids or carbohydrates) antigens bound to MHC on
antigen presenting cells (APC) (also called "professional" cells).
The TCR binds to both the peptide antigen and to parts of the MHC protein |
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Term
| How are protein antigens captured by APCs? |
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Definition
1) Trans-epithelial antigens are captured by DCs and
these activated DCs travel to lymph nodes via lymphatic vessels.
2) Antigens in blood stream circulate and are filtered out by APCs in the Spleen |
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Term
| What is the difference between DCs in peripheral tissues and those in lymph nodes and in the spleen? |
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Definition
-DCs in peripheral tissues such as the skin are immature and are specialized for antigen capture (called Langerhans cells in the skin)
-DCs in lymph nodes and spleen are mature with MHC expression and co-stimulatory molecules
-Maturation occurs during migration of Langerhans cells to T cell rich areas of draining lymph node |
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Term
| What are the 5 mechanisms of Antigen capture by DCs? |
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Definition
1) Macropinocytosis (soluble molecules)
2) Phagocytosis (enhanced by C3b and IgG opsonization)
3) Fc receptor mediated uptake (IgG-coated particles as well as Ab/Ag aggregates)
4) Immune complex uptake (Ab/Ag aggregates via Fc receptors)
5) Receptor mediated endocytosis (fMet-Leu-Phe bacterial sequence) |
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Term
| Explain the different portions of the HLA gene cluster as they relate to MHC presentation. |
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Definition
1) Class 1 MHC encoded by HLA-A, B and C genes
2) Class 2 MHC encoded by HLA-DR, DQ and DP genes as well as proteins important for antigenic presentation (DM, proteasome subunits and Tap 1,2)
3) Class 3 MHC genes include cytokines and complement factors |
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Term
| What is the basic structure of Class 1 MHC proteins and how does it influence their function? |
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Definition
Heavy chain with 3 extracellular domains (alpha 1-3)
B2-microglobulin subunit that binds heavy chain and stabilizes structure
2) Found on all somatic cells and recognized by CD8+ T-cells
3-D structure has platform with homology to Ig constant domains and a binding cleft for peptide**
A single peptide (generally 8-10 AA long) can bind to a single MHC protein, however, there is BROAD SPECIFICITY |
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Term
| What is the basic structure of Class 2 MHC proteins and how does it influence their function? |
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Definition
1) Dimer with 1 alpha and 1 beta chain
2) Found on professional APC=DC, macrophages and B-cells and interact with CD4+ helper T-cells
3-D structure is similar to class 1, with peptide binding cleft, but with subtle differences
Generally bind peptides of 12-20 AA (1 at a time!( that possess peptide binding motif (not necessarily identical sequence) |
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Term
| What does Co-Dominant Expression of MHC genes mean in terms of antigen presentation to T-cells? |
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Definition
| Both parental alleles of each MHC gene are expresses, increasing the number of different MHC molecules that can present peptides to T-cells. |
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Term
| How is MHC-expression dependent upon Antigen availability? |
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Definition
| Only MHC molecules that are displaying peptides (and usually they only bind to peptides) are expressed for recognition by T cells (think of this is saving resources). |
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Term
| What are the 4 basic steps common to both Class I and Class II MHC proteins in terms of Antigen processing? |
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Definition
1) Antigen uptake
2) Antigen Processing
3) MHC biosynthesis
4) Peptide:MHC association |
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Term
| What are the major differences between antigen processing pathways by Class I and Class II MHC proteins? |
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Definition
SHORT
(1= CD8/cytosol/proteosome/ER/TAP)
(2= CD4/endosome and lysosome/Cathepsins/MIIC vesicle, invariant chain DM)
1) Class 1 stimulates CD8+ and Class 2 stimulates CD4+
2) Class 1 gets cytosol protein source and Class 2 gets endosome/lysosome source
3) Peptides are generated by Proteosome in class 1 and by Cathepsins for class 2
4) Class 1 peptide-loading involves ER and Class 2 involves MIIC vesicle
5) Class 1 uses TAP accessory molecule and Class 2 uses invariant chain, DM |
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Term
| Explain how Class II MHC-associated presentation of extracellular antigens to helper T cells occurs. |
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Definition
1) Macrophage with MHC-II engulfs microbe and presents it to CD4 + T-cell, which then releases cytokines leading to Macrophage activation and destruction of phagocytosed microbes
2) Microbial antigen-specific B-cell grabs microbe with Ab and presents it to T-cell, which releases cytokines leading to B cell antibody secretion. |
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Term
| Explain how Class I MHC-associated presentation of extracellular antigens to cytolytic T cells occurs. |
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Definition
| 1) Cells present cytoplasmic microbes to CD 8+ T cells (T-cell priming), which kill the antigen-expression infected cell. |
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Term
| Explain the meaning of "cross-presentation" as it relates to the MHC-I and MHC-2 pathways of antigen presentation. |
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Definition
| Sometimes, bacterial microbes that are taken in to a cell via phagocytosis can be released into the cell cytoplasm and go by the MHC-I/CD8+ pathway, rather then the MCH-II/CD4+ pathway. |
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Term
| How does the body eliminate virus-infected cells? |
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Definition
1) Professional APC (i.e. DC or macrophage) will gobble the cell up and present viral antigens at the cell surface via MHC-I
2) CD8+ T Cells recognize and kill the cell (CROSS PRESENTATION) |
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Term
| Which class of MHC molecules are more diverse and why? |
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Definition
MHC-II
Remember, the peptide-binding site of these molecules is formed by 1 alpha and 1 beta chain, meaning that you get many different combinations of DP, DQ and DR (12 possibilities vs only 6 for the alpha chains of MHC-I) |
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Term
| Where does CD4-binding occur in MHC-II molecules? |
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Definition
| on the beta-2 subunit (support stalk). |
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Term
| Why can MHC-II bind larger antigens than MHC-I (12-20 AA vs. 8-10 AA). |
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Definition
| The peptide-binding pocket of MHC-II, which is composed of 1 alpha and 1 beta chain domain, is larger and deeper. |
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Term
| How does allelic polymorphism influence MHC protein function? |
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Definition
| It ensures that different individuals are able to present and respond to different microbial peptides. |
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Term
| Explain the difference between the exogenous and endogenous pathways of protein antigen capture and presentation. |
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Definition
1)
Exogenous microbes are taken up via endocytosis.
Antigen-containing vesicles fuse with exocytic vesicles containing alpha and beta chains of MHC-II (complex formation is prevented by invariant chain)
Invariant chain is removed by DM and Cathepsin proteases- MHC-II complex forms and binds antigen.
MHC-II/antigen complex is presented to naive, CD4+ Th cells.
2) Cytosolic virus particles and microbes (already unfolded) arrive at the ER and are "tapped" inside by TAP.
Antigens and MHC-1 enter exocytic vesicles and travel to plasma membrane
MHC-I/antigen complex is recognized by CD8+ CTLs, and cells are destroyed. |
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Term
| What is the role of "Tap" in T-cell activation? What would happen if it was missing? |
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Definition
Tap is an important protein in the endogenous antigen presentation pathway.
It is required for antigen-entry into the ER, prior to packaging of antigens into vesicles with MHC-I for presentation to CD8+ CTLs.
W/o Tap, you could not effectively present viral/bacterial antigens to cytotoxic T cells, and infections would run rampant! |
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Term
| What is the role of "Invariant Chain" in T-cell activation? What would happen if it was missing? |
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Definition
Invariant Chain molecules are important for the exogenous pathway of antigen presentation to CD4+ Th cells.
Invariant Chain molecules prevent the alpha and beta chains of MHC-II from joining in the ER, and in doing so prevent self-recognition of ER proteins.
Once antigen-containing endocytic vesicles fuse with MHC-II component-containing vesicles, Invariant Chain is released via the action of DM and Cathepsins, and the MHC-II complex forms and binds up antigens.
W/O invariant chain, you could have self-reactive issues in the ER resulting in autoimmune disease. |
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Term
True or False
MHC complexes only recognize Antigens (including lipids and carbohydrates) |
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Definition
False!
MHC-I mostly recognizes endogenous self peptides. It is only when there is a foreign invader that these cells activate CD 8+ CTLs! |
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Term
| Explain how B-cels can activate C-cell antibody secretion. |
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Definition
Bcell-Tcell-Cytokine-Bcell
1) B-cells present bacterial antigens (extracellular microbes) to CD4+ Th cells.
2) The helper T-cells release Cytokines, which stimulate B-cell Ab production and binding to microbes. |
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