Immunoglobulins and Antibody: Structure and Function

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Immunoglobulins and Antibody Structure and
Function

• January 30, 2001

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Outline

• Immunoglobulin Structure
• Variable Region Domains
• Constant Region Domains
• Immunoglobulin Classes
• Immunoglobulin Function
• Antigenic Determinants
• The B Cell Receptor
• The Immunoglobulin Superfamily

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Antibodies

• Membrane-bound versus Soluble
• Membrane-bound antibody confers antigen
  speci-ficity, binds antigen, leads to B cell
  activation
• Soluble antibody circulates in blood, binds to
  antigen, neutralizes it or marks it for
  elimination
• Polyclonal versus Monoclonal
• Antigens have multiple epitopes and elicit
  multiple (polyclonal) antibody responses from
  multiple B cells
• For research and clinical applications, a single
  (monoclonal) antibody response is preferable

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http//www.bio.davidson.edu/Biology/Courses/RasMol
.html
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Sequencing of Antibodies Multiple Myeloma

• Multiple Myeloma Cancer of antibody-producing
  plasma cells
• Uncontrolled growth and secretion of antibody
  molecule (myeloma protein)
• Up to 95 of serum Ig in some patients
• Excess light chain (Bence-Jones protein)
  secreted, as well

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Outline

• Immunoglobulin Structure
• Variable Region Domains
• Constant Region Domains
• Immunoglobulin Classes
• Immunoglobulin Function
• Antigenic Determinants
• The B Cell Receptor
• The Immunoglobulin Superfamily

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Outline

• Immunoglobulin Structure
• Variable Region Domains
• Constant Region Domains
• Immunoglobulin Classes
• Immunoglobulin Function
• Antigenic Determinants
• The B Cell Receptor
• The Immunoglobulin Superfamily

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Immunoglobulin Function

• Binding versus Effector Function
• Opsonization (Phagocytosis promotion) Fc
  receptors (FcR) on phagocytes
• Complement Activation Cell membrane damage C3b
  binding to antigen/antibody complex C3b
  receptors on mf and RBCs
• Antibody-Dependent Cell-Mediated Cytotoxicity
  (ADCC) NK cells bind Ag/Ab complex via FcR,
  induce apoptosis

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Outline

• Immunoglobulin Structure
• Variable Region Domains
• Constant Region Domains
• Immunoglobulin Classes
• Immunoglobulin Function
• Antigenic Determinants
• The B Cell Receptor
• The Immunoglobulin Superfamily

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Antigenic Determinants
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Outline

• Immunoglobulin Structure
• Variable Region Domains
• Constant Region Domains
• Immunoglobulin Classes
• Immunoglobulin Function
• Antigenic Determinants
• The B Cell Receptor
• The Immunoglobulin Superfamily

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The B Cell Receptor

• mIgs have short cytoplasmic tails (3-28 a.a.)
• mIgs signal via association with Ig-a/Ig-b
  heterodimer
• Ig-a/Ig-b heterodimer can complex with
  intracellular signalling molecules (e.g. tyrosine
  kinases, G proteins)

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Outline

• Immunoglobulin Structure
• Variable Region Domains
• Constant Region Domains
• Immunoglobulin Classes
• Immunoglobulin Function
• Antigenic Determinants
• The B Cell Receptor
• The Immunoglobulin Superfamily

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The Immunoglobulin Superfamily

• Many membrane-bound proteins have
  Immunoglobulin-like domains
• Derived from distinct genes which all arose from
  a common ancestor gene
• Most do not bind antigen
• Examples include
• Ig-a/Ig-b heterodimer
• T Cell Receptor (TCR)
• MHC Class I and MHC Class II molecules
• CD2, CD4, CD8, CD28, CD3g/d/e, some adhesion
  molecules

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..see you Thursday!