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57 Cards in this Set
- Front
- Back
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What is the most important distinction between class I and II antigen presentation?
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The source of peptides
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What samples the cytoplasm of cells?
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Class I
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What samples the extracellular areas?
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MHC II
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5 things that must happen for Class I antigen presentation:
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1. Tag proteins
2. Proteolysis 3. Delivery of peptides to MHC I 4. Binding of peptide to MHC I 5. Display of Ag/MHC to T cell |
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What tag is used to target intracellular proteins for degradation?
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Ubiquitin
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What residue does Ubiquitin bind?
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Lysine
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What degrades peptides after polyubiquitination?
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A proteosome
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What is an immunoproteosome?
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A proteosome that has had 3 beta subunits in its core replaced with LMP's encoded in MHC
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What stimulates the replacement that makes an immunoproteosome?
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IFN-y produced from NK cells and T cells during viral infections
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Do proteosomes only degrade antigenic material?
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No - every single protein in the cell is subject to turnover.
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How big is the diameter of the center of a proteosome?
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13 angstroms
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What has to happen to proteins before they can be degraded by the proteosome core?
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After the CAP recognizes the poly-Ub tag, it must be removed by isopeptidases
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What size of residues are generated by the proteosome?
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4-20 AA long
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What size peptides does MHC I fit?
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8-10 AA long
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Where in cells are proteasomes located?
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In the cytoplasm
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Where is Class I MHC made?
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In the ER
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So how do proteins degraded in the cytosolic proteasome get in contact with Class I MHC in ER?
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Via TAP transporter
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What does putting peptides into the ER with TAP allow?
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Stable uniting of the MHC heavy chain with B2m and peptide.
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Where is TAP encoded?
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Within MHC
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What type of protein substrates does TAP select for?
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Those ending in LIVM, and 6-15 residues long
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What molecules link TAP to MHC I and aid during transfer of the peptide in the ER?
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Tapasin - links TAP to MHC I
Calreticulin/Calnexin - chaperones that aid too. |
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Does MHC I only present foreign antigenic peptides on its surface?
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OF COURSE NOT! It presents self peptides all the time, on healthy cells.
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If self antigen is being presented on MHC I to Tc cells all the time, how come all nucleated cells don't die then?
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Because Tcells that would react to self antigen are eliminated during thymic education.
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What is alloreactivity?
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The reaction of our own T and B cells to nucleated cells in transplanted tissue, which though it presents self Ag, uses foreign MHC to do it.
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What length of peptides are presented by Class I MHC again?
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8-10 residues
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What length of peptides are presented by Class II MHC?
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10-16 residues, but can be up to 30 residues!
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What is the source of peptides presented by Class II MHC?
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Extracellular
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How do the extracellular proteins get into the cell?
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By endocytosis
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How are the endocytosed proteins degraded into peptides?
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By lysosomal enzymes
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What are the lysosomal proteases that chop up microbial proteins called?
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Cathepsins
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What is required for Cathepsins to be active?
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pH=5 within lysosome
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Where is Class II MHC made?
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In the ER
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How come Class II MHC doesn't get loaded with peptides bound for Class I MHC?
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-Peptides bound for Class I MHC are bound to TAP and need tapasin to link them together.
-Class II MHC is satisfied with invariant protein |
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What purpose does Invariant chain serve other than preventing peptide loading onto MHC II prematurely?
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Its dileucine motif serves as a zipcode to sort MHC II to lysosomes rather than the default presentation pathway.
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In what exact form does Class II MHC travel from the ER to lysosomes?
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As a trimer composed of 3 MHCII molecules and 3 invariant chains.
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Where does invarient chain contact MHC II?
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it binds right in the binding cleft
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What is the final state of invariant chain once MHCII gets to the lysosome?
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It is cleaved and leaves a CLIP bound in the binding cleft.
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What is responsible for exchanging antigenic peptide in place of CLIP on MHC II in lysosomes?
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HLA-DM
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After CLIP is dislodged from MHC II's binding cleft, what does HLA-DM do?
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Keeps bumping antigenic peptides out of the cleft until one fits so perfectly that it can't be jarred.
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What happens to MHC II if a peptide doesn't bind well enough and HLA-DM keeps jarring them out of the groove?
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Without peptide MHCII is unstable, it unfolds, and is destroyed by proteases in the lysosome.
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Can self peptides be presented on MHC II to CD4 pos Thelper cells?
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YES
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Can self peptides be presented on MHC I to CD8 pos Tcytotoxic cells?
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uhhhh YES
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What is Cross-presentation?
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The presentation of extracellular peptides on MHCI
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What cells are capable of cross presentation?
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Only specialized APC's
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Are MHCI and MHCII the only antigen presenting molecules?
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NO; also CD1 can do it
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What class of MHC does CD1 resemble most? Why?
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Class I - it binds B2-microglobulin and has a similarly shaped groove.
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What type of antigen is presented by CD1?
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LIPID (not peptide)
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Is CD1 encoded within MHC?
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no
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What cells possess CD1?
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only APCs
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What cells possess MHCII?
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only APCs
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What cells are capable of cross-presenting?
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only APCs
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What cells have MHC I?
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All nucleated cells
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What do APCs with CD1 present lipid TO?
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CD1-specific T cells
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How does CD1 travel when not lipid-bound?
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With invariant chain
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What are the 3 main types of specialized APCs?
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1. B cells
2. Dendritic cells 3. Macrophages |
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What cells can be induced to become APCs?
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Keratinocytes and some others
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What induces keratinocytes to become APCs?
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IFN-y
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