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Janeway's Immunology

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Title: Janeway's Immunology


1
MICR 304 Immunology Serology
Lecture 7B Antibodies Part I Chapter 3.1 3.9
2
Overview of Todays Lecture
  • Basic structure of antibodies
  • Generation of antibodies
  • Structural variations in the constant regions

3
Key Players in Immunology
Innate Adaptive
Cells Phagocytes Epithelial Cells NK Cells Lymphocytes (B-Ly, T-Ly)
Effector Molecules Complement Antimicrobial (Poly)Peptides Antimicrobial lipids? Antibodies
4
What is an Antibody?
  • Glycoprotein
  • Binds to antigen
  • Consists of 2 heavy chains (m,d,g,a,e) and 2
    light chains (k,l) connected by disulfide bonds
  • Variable domains (antigen binding)
  • Constant regions (effector function)

5
Antibody Classes
  • Determined by the type of constant chain
  • g IgG
  • m IgM
  • a IgA
  • e IgE
  • d IgD

Used to explain principle make up of an ab
6
Basic Structure of an Antibody Molecule
  • 2 light and 2 heavy chains
  • Disulfide bonds
  • Hinge region
  • N-terminus variable, antigen binding
  • C-terminus constant region, effector function

7
Proteolytic Cleavage of the Antibody Molecule
  • Variable regions intact
  • Antigen binding without effector function

Single site
  • Constant regions intact
  • Crystallizable

pepsin
  • Variable regions intact and additional amino
    acids
  • Antigen binding without effector function

Multiple sites
8
Antibody Molecules are Flexible
Spikes Disappear after treatment with pepsin
Antibody arms are joined by a flexible hinge.
9
The Structure of Immunoglobulin Constant and
Variable Domains
Anti-parallel b strands forming 2 b sheets that
assume a b barrel structure
Immunoglobulin superfamily domain (4 strand 3
strand) of (4 strand 5 strand) Found in many
other proteins
V domain is larger!
10
Localized Regions of Hypervariable Amino Acid
Sequences Form the Antigen Binding Site
Variability Plot
Compares aa sequences of many different V regions
  • Hypervariable regions (HV1-3) of light chain and
    heavy chain create the antigen binding site
  • Surface complementary to the antigen
  • Complementarity-determining regions (CDRs)
  • Combinatorial diversity
  • Framework regions (FR1-4) provide structural
    frame work

11
Hypervariable Regions Lie in the Discrete Loops
  • Different aa in different CDRs form different
    surfaces and bind different antigens.

12
Antigen Binding Sites Assume Varying Shapes
Groove
Extended Surface
Pocket
Protruding Surface
13
Hapten
  • Antigen that is too small to elicit antibody
    response by itself
  • When coupled to carrier protein antibodies can be
    generated
  • Once antibodies are generated they can recognize
    and bind to uncoupled hapten

14
Epitop
  • Domain on antigen which actually binds to
    antibody binding site
  • Antigenic determinant
  • Two types of epitops
  • Conformational
  • discontinuous aa sequence
  • Linear
  • continuous aa sequence

Y
Y
15
Non-Covalent Forces in Antigen-Antibody
Interactions
(Salt bridges)
Overall interaction
(Electric dipoles)
Short distance
16
Antibody-Antigen Interactions
  • Never covalent!
  • Reversible
  • Depends on the actual antigen and antibody
  • Single amino acid changes can cause loss of
    recognition

17
Light Chain
Heavy Chain
Glutamine residue (Ly) making hydrogen bonds
Lysozyme
18
Active Learning Exercise
  • How can the interaction between antibody and
    antigen be disrupted and antigen released from
    the antibody?

19
Todays Take Home Message
  • The IgG antibody molecule consists of 2 identical
    light chains and 2 identical heavy chains
    connected by disulfide bridges.
  • Each chain contains at the N-terminus a variable
    region for antigen binding and at the C-terminus
    a constant region for effector function.
  • The variable regions of the light and heavy chain
    form antigen binding sites.
  • Each antibody molecule has two identical antigen
    binding sites allowing for cross linking of
    antigen.
  • Hypervariable loops comprise the complementarity
    determining regions that form the surface
    interacting with the antigen
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