Structure of Antibodies and BCR

Structure of Antibodies and BCR

• B Cell Receptor (BCR) is an antibody functioning as a receptor on B cells.
• T Cell Receptor (TCR) is found on T cells and does not secrete antibodies.

Serum Antibodies

• Activated B cells, known as plasma cells, produce serum antibodies.
• Antibodies, also referred to as immunoglobulins (Ig), are glycoproteins essential for immune functions.
• There are 5 main classes (isotypes) of antibodies:
  • IgG (Gamma) - 5 constant regions
  • IgM (Mu) - 5 constant regions
  • IgA (Alpha) - 4 constant regions
  • IgE (Epsilon) - 4 constant regions
  • IgD (Delta) - 4 constant regions
• Each class has subisotypes, denoted as Ig1, Ig2, etc.

Antibody Structure

• Antibodies have a Y-shaped structure consisting of two arms, with 4 total polypeptide chains: 2 light chains and 2 heavy chains.
• Chains are held together by disulfide bonds.
• Each antibody features:
  • A hinge region that provides flexibility in binding.
  • Antigen binding sites specific to one epitope.
• IgG, IgA, and IgD contain a hinge region; IgM and IgE do not but can still exhibit flexibility.

Functional Structure

• Each antibody (monomer) has 2 antigen binding sites originating from the variable domains of heavy and light chains, referred to as the Fab region.
• Antibodies activate complement and bind to phagocytes through the constant region known as the Fc region; this interacts with Fc receptors on effector cells.

Proteases in Antibody Study

• Proteases are used to explore antibody structures and in immune diagnostics.
• Two key proteases:
  • Papain: Cleaves antibodies into 2 Fab and 1 Fc fragments.
  • Pepsin: Cuts below the hinge region, producing F(ab)2 fragments (can bind antigens but lack biological activity).

Genetic Engineering and Domain Structure

• Single chain antibodies feature only the variable region, known as Fv (fragment variable).
• Antibodies share a conserved structure, including amino acid sequences and a beta barrel or beta sandwich arrangement attributed to the immunoglobulin (Ig) domain.
• Disulfide bonds between beta strands contribute to the stability of the structure.

Hypervariable Regions

• Most variability in immunoglobulins resides in the variable regions, specifically the three hypervariable regions (HV1, HV2, HV3).
• The specificities of antibodies result from differences in these hypervariable regions among various antibodies.

Complementarity Determining Regions (CDR)

• Each arm of an antibody contains three complementarity determining regions (CDRs), formed by the combination of hypervariable regions from both light and heavy chains.
• CDRs play a crucial role in determining the specificity of antibody-antigen interactions.