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Describe the structure of IgG antibodies
- Consist of 4 polypeptide chains (two identical heavy chains and two identical light chains)
- Disulfide bonds link the heavy chains to eachother and the heavy chains to the light chains
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Describe avidity vs affinity
- avidity: strength of simultaneous binding to 2 identical antigens
- affinity: strength of interaction between a single antigen-binding site and its antigen
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What are the 5 heavy-chain classes for immunoglobulin? Brief structure and function
- Only vary in the constant region of Ab - variable region looks similar for all ("V shape")
- IgM: First class produced after B cell activation
- secreted as pentamer (huge) - not in tissues
- lysis and agglutination
- IgG: most common (blood and tissues)
- Y shape
- opsonization
- IgA: secreted in mucosal surfaces, mothers milk, etc
- dimer + J chain and secretory component
- blocks entry of microorganisms
- IgE: defense against multicellular parasites
- bind to mast cell/basophill (allergy)
- IgD:
- function unknown
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What are the two light chain types for immunoglobulin?
- λ (lambda) and κ (kappa)
- B lymphocytes express only one type that remains fixed for its life
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Protein domain vs protein motif
- Domain: compactly folded region of protein structure
- Motif: sequence of AA w/ unique f(x) found within a domain
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What proteases can be used to cleave an antibody and into what fragments?
- papain: 2 Fab fragments + 1 Fc fragment
- pepsin: 1 F(ab')2 fragment + many small pieces of Fc fragment
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What are the two types of flexibility in an antibody molecule? What is the benefit?
- At the hinge
- At the junction between the V and C domains
- The antibody can bind to repeated antigens that are not directly adjacent
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What is the name for the varying regions and constant regions in the V region of an antigen, and how are they related to its secondary structure? Is there an alternate (more appropriate) name for the varying regions?
- There are three hypervariable regions (HV1, HV2, HV3) surrounded by framework regions (FR1, FR2, FR3, FR4)
- The framework regions form the β sheets (structure framework)
- The hypervariable regions form the outer edge of the β barrels (point of contact for antigens) and are termed complementarity-determining regions (CDRs) (CDR1, CDR2, CDR3)
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What are the two kinds of epitopes?
- Continuous or linear: single segment of a peptide chain
- Conformational or discontinuous: discontinuous sequentially, but nearby due protein folding
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Describe the structure of a TCR. How do they differ from BCR?
- Each T cells has ~30,000 identical TCR
- T-cell receptors are heterodimers (α chain and β chain)
- The αβ heterodimer is analogous to the Fab fragment of an antibody
- Unlike BCR, TCR have only one antigen binding site and are never secreted
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Describe the molecular structure of MHC I and MHC II molecules
- MHC I: 2 polypeptide chains (only α spans membrane)
- α - forms 3 domains (α1, α2, α3)
- α1 and α2 form the peptide binding cleft
- β2-microglobulin - forms 1 domain, noncovalently associated with the α chain
- MHC II: 2 polypeptide chains (both span membrane)
- α - forms 2 domains (α1, α2)
- β - forms 2 domains (β1, β2)
- α1 and β1 form the peptide binding cleft
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What types of molecules does MHC I bind? How does it stabilize such a variety of molecules?
- short peptides (8-10AA)
- stabilized at both ends of the peptide-binding cleft by invariant sites (Tyrosine residues)
- Variations in length are accommodated by kinking the peptide backbone
- Varying peptides can bind due to conserved "anchor residues"
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What is the difference between an anchor residue and a conserved polymorphic residue?
- Anchor residue: similar amino acid residues in specific positions on a peptide
- Conserved polymorphic residue: residues on an MHC molecule that interact with anchor residues
- conserved in a given MHC molecule, but polymorphic in a population
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What types of molecules does MHC II bind? How does it differ from MHC I binding? How does it stabilize such a variety of molecules?
- longer peptides (13+ AA)
- No conserved Tyr residues (the ends of a peptide are not bound)
- Polymorphic residues' interactions with anchor residues hold the peptide in place
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What are the two T cell co-receptors? What types of cells have them? Which MHC molecules recognize them?
- CD4: helper T cells, MHC II
- CD8: cytotoxic T cells, MHC I
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Describe the structural difference between CD4 and CD8 co-receptors. How do they function?
- CD4: single chain of 4 Ig-like domains (D1-D4)
- CD8: dimer of 2 chains (α and β) that each link to the membrane
- Both bind Lck (a cytoplasmic tyrosine kinase) on MHC and bring it close to the TCR, increasing sensitivity by ~100x
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On what cells can MHC I and II molecules be found? Why?
- MHC I: expressed on all nucleated cells
- used to express viral infection
- MHC II: expressed on B lymphocytes, dendritic cells, and macrophages (APCs)
- activate B cells/macrophages
- induce naive helper T cell maturation
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What regulates MHC I and II expression? Specifically what regulates each and how?
- Interferons released during immune response
- IFN-α and IFN-β increase MHC I expression in all cell types
- IFN-γ increases MHC I expression in virus-infected cells and MHC II expression in macrophages and other cells which may not normally express MHC II
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