Antibody Structure and Function

  • Fab (containing the variable/hypervariable regions) consisting of light (L) and heavy (H) chains recognizes antigens. Fc region of IgM and IgG fixes complement. Heavy chain contributes to Fc and Fab regions. Light chain contributes only to Fab region.
  • Fab:
    • Fragment, antigen binding
    • Determines idiotype: unique antigen-binding pocket; only 1 antigenic specificity expressed per B cell
  • Fc:
    • Constant
    • Carboxy terminal
    • Complement binding
    • Carbohydrate side chains
    • Determines isotype (IgM, IgD, etc)
  • Generation of antibody diversity (antigen independent)
    1. Random recombination of VJ (light-chain) or V(D)J (heavy-chain) genes
    2. Random addition of nucleotides to DNA during recombination by terminal deoxynucleotidyl transferase (TdT)
    3. Random combination of heavy chains with light chains
  • Generation of antibody specificity (antigen dependent)
    1. Isotype switching (constant region) – occurs in naïve B-lymphocytes upon initial exposure to antigen.
    2. Affinity maturation through somatic hypermutation. DNA coding for the immunoglobulin variable region is mutated randomly at a very high rate. Cells that exhibit a stronger affinity for the antigen are able to proliferate more than cells with lower affinity.

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