03+Immune+Receptors+Part+1+PRE.pptx

03+Immune+Receptors+Part+1+PRE.pptx - Immune Receptors...

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Immune Receptors, Recognition, and Response
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What We’ll Cover Receptor-Ligand Interactions B and T Cell Receptors Innate Immune Receptors Cytokines and their Receptors Signaling Pathways Triggered by Immune Receptors
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Receptor-Ligand Interactions Immune cells express numerous types of receptors and must integrate multiple simultaneous (or sequential) signals Pattern Recognition Receptors expressed on both innate immune cells and adaptive immune cells (B & T cells) B and T cells also express their unique antigen-specific receptor Immune cells also express cytokine and chemokine receptors (for cell- cell communication) Receptor affinity, expression levels, and locations, can vary based on activation status of the cell
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Receptor Ligand Interactions Receptor-ligand binding occurs via multiple noncovalent bonds Each individual interaction quite weak Numerous interactions between receptor and ligand makes cumulative interaction very strong Noncovalent interactions only occur over very short distances (~1Å = 10 -10 meters) so receptors/ligands need to have very close fit (high complementarity)
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Multivalent Receptor-Ligand Interactions Noncovalent interactions inherently reversible: ligands constantly bind and unbind their receptors Bound ligands = “on”; Unbound = “off” In monovalent/univalent receptors (just one binding site), ligand is either completely on or off In multivalent receptors (multiple binding sites), less likely that all receptor sites simultaneously off. Interaction with ligand not completely lost Monovalent receptor is either ON or OFF Bivalent Receptor: Even if one binding site is OFF, other binding sites remain ON
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Receptor-Ligand Complex ( RL ) Receptor ( R ) Ligand ( L ) + Association Rate ( k 1 ) Dissociation Rate ( k -1 ) Association Constant ( K a ) (= affinity , units M -1 ) the higher the K a , the higher  affinity of the interaction K a = [R][L] [RL] k -1 k 1 = Dissociation Constant ( K d ) (units M) the lower the K d , the higher  affinity of the interaction K d = [R][L] [RL] k -1 k 1 = Receptor-Ligand Interactions: Affinity
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Rank the following interactions from highest to lowest affinity Receptor Ligand K a  (M -1 ) K d  (M) T cell receptor (2B4, CD4 + T Cell) MHC bound to peptide (MCC/E k ) 0.05 T cell receptor (42.12, CD8 + T Cell) MHC bound to peptide (OVA/K b ) 153.85 anti-Antigen A Antibody (start of immune response) Antigen A 3x10 -5 anti-Antigen A Antibody (late in immune response) Antigen A 5x10 10
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Receptor-Ligand Interactions: Valency & Avidity Valency: The number of binding sites available Avidity: Overall strength of binding in a multivalent interactions e.g. when multiple antigen-binding sites on an antigen interact with multiple regions (epitopes) on an antigen Secreted Immunoglobulin  (Antibody) = antigen binding site bivalent T Cell Receptor (TCR) monovalent
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Surface Receptors Cluster When Binding Multivalent Ligands Multivalent antigens have more than one binding site, allowing multiple receptors to bind them Multiple monovalent receptors can be bound to multivant ligand Multivalent interactions increase avidity
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  • Spring '18
  • Adrianne Vasey
  • NK Cell

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