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Unformatted text preview: Immunology 12-Endogenous Pathway of Antigen Processing and Presentation • Variable region of Ab is similar to variable region of CR; both use the variable regions to form an antigen binding site • TCR does not have a Fc region • TCR is similar to an Fab fragment of antibody • Y:δ T cell receptors have different antigen recognition properties from the a:B T cell receptors • Stalk segment has a cysteine residue that forms the interchain disulfide bond; short stalk is homologous to the Ig hinge region; alpha chain has 2 positive residues in the hydrophobic domain, the B chain only has 1 • In the C alpha domain the intramolecular disulfide bond joins a B strand to this segment of alpha helix • Interface between the C and V domains of both T-cell receptor chains is more extensive than in most Abs • The C alpha domain doesn’t fold into a typical Ig domain; the face of the domain away from the C beta domain is mainly composed of irregular strands of polypeptide rather than B sheet; sugar groups on C alpha make hydrogen bonds with C beta domain • Differ from B cell receptor: has only ONE Ag binding site and TCRs are never secreted • 1 type of T-cell receptor on each T-cell • TCR: alpha chain and beta chain joined by disulfide bridge; extremely short cytoplasmic tail so it must use co-receptors; variable and constant regions; variable region has surface that recognizes 3D conformation of antigen but is different from B-cell recognition TCR antigen recognition • T cells (via T cell receptors) only recognize foreign antigens displayed on the surface of the body’s own cells • Respond to short continuous amino acid sequences; often buried within the native structure • T cell interacts with the ligand by making contacts with both the MHC molecule and the antigen peptide • Antigen is displayed as peptide fragments bound to MHC molecules • Peptides can stimulate T cells only when bound by MHC—the phenomenom is called MHC restriction (limiting) • Different MHC molecules (encoded by different genes as well as by different alleles of genes) have specific differences in what subset of peptides they are able to present to T cells • Only linear peptides! No globular proteins, phenols etc MHC restriction • T cell recognizes a specific peptide and MHC combination; it won’t recognize the same peptide on a different MHC molecule or a different peptide on hte same MHC molecule • Recognizes surface of peptide/MHC molecule MHCI/MHCII • MHC molecules have peptide binding clefts • Class I: binding cleft formed by alpha1/alpha2 subunits; floor formed by B2-microglobulin; alpha chain is noncovalently associated with the B2 unit; alpha 3 and B2 closely resemble Ig like domains in their folded structure; the sides of the cleft are formed by the inner faces of the 2 alpha helices; the B pleated sheet formed by the pairing of alpha 1 and alpha 2 creates the floor of the celft • Class II: bigger opening on binding cleft that MHC I; important for binding differentiation in peptide binding; 3D cleft is similar to MHCI...
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This note was uploaded on 02/08/2012 for the course PATHOLOGY 3245 taught by Professor X during the Spring '11 term at UWO.
- Spring '11