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TEACHER
Activity: Modeling antibody structure using Chenille Stems
Objective: This activity describes a way to model the basic structure of antibodies. The model uses
chenille stems to show the basic layout of an antibody: the 2 heavy chains, 2 light chains,
and the disulfide bonds that hold those polypeptides together. The model is then used to
demonstrate the vast diversity in the variable regions of antibodies using VDJ
recombination.
Estimated Time: 20-30 minutes
Extensions: This activity can be extended by completing the Protein Data Bank activity
(http://www.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month
/alphabetical_list.html). The Protein Data Bank activity requires online computer
access.
Materials needed (32 students):
 2 whole pipe cleaners of the same color (heavy chain segments)
 1 pipe cleaner cut into 2 pieces (light chain segments)
 1 “sparkle” pipe cleaner cut into 4 pieces (disulfide bonds)
 Container of colored beads to use as VDJ segments
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64 total
32 total
32 total
320 total
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Important concepts:

Antibodies are made of 2 heavy chain
polypeptides (blue in the diagram) and 2
light chain polypeptides (red in the
diagram). Each chain is a polymer of amino
acids.

Disulfide bonds (S-S bonds between
cysteine residues) hold the 4 chains
together. Two disulfide bonds connect the
heavy chains together, while one disulfide
bond connects each light chain to the
nearest heavy chain.

The antibody takes on a Y-shape when all 4
chains interact.
From:
http://chemistry.umeche.maine.edu/CHY431/Antibody.jpg

The trunk of the “Y” makes up the constant region of the antibody and is specific to each
species. The arms of the “Y” on the antibody make up the variable region and form a
specific shape that recognizes and binds to one unique epitope (specific region of an
antigen).

Each mature B cell produces antibodies that recognize only one target. There are only
about 21,000 human genes total, so how are millions of different antibodies created when
there aren’t millions of different genes?

Our B cells create tremendous variety in antibody structure from three genes (two that
code for light chains, one that codes for heavy) using a special mechanism called VDJ
recombination.

When a B cell is immature the heavy chain gene contains multiple V segments, D
segments, and J segments, and the light chain gene contains multiple V and J segments.
Heavy chain DNA in immature B cell:
V1 V2 V3 …V51
Variable
segments
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D1 D2 …D27
J1 J2 …J6
Diversity
segments
Joining
segments
C
Constant
segment
2

As immature B cells mature, one V segment, one D segment, and one J segment are
selected at random and recombined into a revised, shorter heavy chain gene. A similar
process occurs in the light chain gene (no D segment is present in this chain).

In mature B cells these shorter genes will provide the instructions for producing the
heavy and light chain polypeptides that compose the structure of the unique antibody.
Creating the Antibody Model
Part One: Building the heavy and light chains
1. Select 4 chenille stems:
a. Two of the same color (heavy chains)
b. One of a color different from the heavy chains (will become light chains)
c. One “sparkle” pipe cleaner (will become disulfide bonds)
2. Lay the two same-colored pipe cleaners side by side on a desk.
3. Cut the third pipe cleaner in half and lay alongside the outside of the two large ones
aligned at the top.
4. Cut the “sparkle” pipe cleaner into 4 even pieces – use two pieces to join the heavy
chains together at the lower half (the “constant region”) of the pipe cleaners, and one
to join each light chain to a heavy chain.
5. Bend the heavy chains apart in a “Y” shape.
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Part Two: Modeling VDJ recombination
1. Randomly choose three colored beads from the container, then select the same three
colors again so they have a pair of each– each colored bead represents one V, one D,
and one J segment on the heavy chain.
2. Place three of the beads in a row on the variable region of one of the heavy chains,
then create the same pattern of beads on the other heavy chain variable region.
3. Randomly choose two more beads from the container (these represent the V and J
segments on the light chain), place them on the end of the light chain. Repeat with the
same two colors for the second light chain variable region so that both light chains
match.
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Part Three: The Discussion
1. Are there any two groups of students who have the exact same colored beads on their
model? (the color of the pipe cleaners does not matter in this model)
2. There are only 10 different colors of beads in the container. How many varieties of
antibody might you be able to create?
a. Heavy chain: (10 V segments) X (10 D segments) X (10 J segments) = 1000
possible combinations
b. Light chain: (10 V segments) X (10 J segments) = 100 possible combinations
c. (1000 possible heavy chains) X (100 possible light chains) = 100,000 possible
antibody variations
3. Now how about the real thing:
a. Heavy chain: (51 V)(25 D)(6 J) = 7650 possible combinations
b. Light chains: (40 V)(5 J) + (31V)(4 J) = 324 possible combinations
c. (7650 possible heavy chains) X (324 possible light) = 2,478,600 possible
combinations
d. BUT WAIT!! Because of additional recombination events and mutations
during mitosis, the actual number of possible antibody variations is potentially
much greater than 1X108 (see the Nature Article: The Double Helix and
Immunology).
Figures created by Tracey Kwong, MCB Student Summer 2007
Adapted from Biological Science, 2nd edition, 2004, by Scott Freeman (Prentice Hall)
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