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22 Cards in this Set
- Front
- Back
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Which amino acids of the antigen peptide bind to the MHC I molecule?
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Amino acids P2 and P9 bind to binding pocket B and F, respectively.
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How do the charges of the binding pockets relate to the charges of the P2 an P9 amino acids of the antigen peptide?
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Amino acids on the peptides and the pocket binding sites are oppositely charged.
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How many amino acids compose the binding pockets found on MHC molecules?
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Pockets B and F are made up of 8 amino acids.
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For HLA-B7,HLA-B27, HLA-B35 what amino acids bind at P2 and P9?
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For HLA-B7 Proline binds at P2, Leucine at P9. For HLA B27 Arg binds at P2 and Lys/Arg/Tyr/Leu at P9. HLA-B35 binds Pro at P2 and Tyr at P9
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How do HLA types influence immune responsiveness?
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MHC alleles regulate immune responsiveness by influencing the number of peptides in a protein that can be recognized. HLA has a lot of variability in binding at the P9 position. It can there for recognize more peptides of an antigen protein and mount an immune defense.
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How are the proteins loaded onto MHC molecules?
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Class I MHC has cytosolic peptides from virally infected cells. Class II MHC have peptides made via lysosomal degradation of endocytosed organism
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Where are MHC I molecules made?
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MHC Class I molecules made in the ER where they bind cytosolic peptides transported to the ER. The peptide-MHC complex is exported to the membrane.
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How does MHC I-antigen complex formation occur in the ER?
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Scaffolding molecules, Calnexin and Colreticulin, hold the nascent MHC molecule in place and keep it open. B2 microglobulin binds to MHC I. Cytosolic peptide fragments produced from cytosolic proteins are transported to the ER via TAP. Binding of TAP with antigen completes folding of MHC I molecule.
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How are cytosolic peptides processed?
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cytosolic proteins are degraded by a proteosome which cuts at the C-terminal with ER cutting at N-terminal. Results in 9AA peptide.
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What is the proteosome composed of?
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Catalytic core and regulatory complexes.
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How does the immune response affect cytosolic processing of proteins?
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IFN-gamma induces the expression of 3 new proteosome subunits that preferentially cleave proteins so that they bind with greater affinity to MHC I molecules. Subunits: LMP1, LMP7, and MECL-1. This is an adaptation that is targeted by viruses
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What is the basic challenge of making Class I and Class II MHC side by side?
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MHC class II do not pick up cytosolic peptides.
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How are peptides destined to bind MHC I proteins kept from binding MHC II molecules?
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Invariant chain (Ii) complexes with MHC molecules during their synthesis in the ER, blocks the class II binding groove of new MHC molecules. Recognition sequence on Ii redirects the MHC class II molecule to an acidic endosomal compartment where it is loaded with degraded ingested exogenous peptides.
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How does binding of antigen occur on MHC II molecules?
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In the endosomal compartment, Ii is chopped off to become CLIP (class II associated invariant chain peptide). HLA-DM (non-polymorphic Class II molecule) relaxes the MHC II molecule and catalyzes binding of antigen.
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How does MHC II antigen loaded molecule get transported to the plasma membrane?
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Once the Ii is cleaved in the endosomal compartment the MHC molecule is trafficked to the PM
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Where are the genes for class I and class II MHC molecules found?
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Both are found on the short arm of chromosome 6.
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How many different types of class I molecules are expressed on the surface of each cell?
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Due to co-dominant expression of MHC Class I molecules from each parent, there are 6 different types of class I molecules on the surface of each cell. HLA-A, HLA-B, HLA-C
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How many molecules of each class I type are expressed on the membrane?
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10,000-20,000 of each type are present on most cells.
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What is linkage disequilibrium?
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The increased chance of certain alleles showing up together within a population.
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How many different types of class II molecules are expressed on the surface of each cell?
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Due to co-dominant expression and the fact that MHC II molecule is composed of two alpha and two beta chains. you get 4 different types for both HLA-DQ and HLA-DP. For HLA-DR you get 2 different types because of the monomorphic nature of HLA-DRA. 10 MHC II types in total.
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What portion of the MCH-peptide complex does the TCR interact with?
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It interacts with both the peptide and the MHC molecule. The CDR3 hypervariable region of TCR interacts with the peptiden
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What does it mean to say that T-cell recognition is both MHC restricted and antigen specific?
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The TCR has to interact with the MHC molecule and the peptide. It needs to recognize the peptide (i.e be specific) and the MHC molecule (MHC restricted) in order to bind the cell presenting the antigen (APC or other cell)
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