Biomedical Engineering Reference
In-Depth Information
a
b
Control
Single knockout
200
200
Clone 1
Clone 2
Clone 3
Clone 4
Clone 5
150
150
100
100
50
50
0
0
0
5
10
15
0
5
10
15
Time (days)
Time (days)
c
d
Double knockout
Triple knockout
200
200
150
150
100
100
50
50
0
0
0
5
10
15
0
5
10
15
Time (days)
Time (days)
Fig. 6
Basic immunodominance model: time evolution of effector cell clones for Scenario 1. Five
T cell clones are present at the same initial concentration
K
i
(
0
)=
0
.
01 k/
μ
L and reactivities
p
1
=
1
32. All other parameters are taken from Table
1
.
(
a
) Control experiment: clones 1-5 all respond. (
b
) SKO: clone 1 is removed. Only clones 2-5
respond. (
c
) DKO: clones 1 and 2 are removed. Only clones 3-5 respond. (
d
) TKO: clones 1-3 are
removed. Only clones 4 and 5 respond
/
2,
p
2
=
1
/
4,
p
3
=
1
/
8,
p
4
=
1
/
16, and
p
5
=
1
/
double knockout (DKO), and triple knockout (TKO) experiments in which the T
cell responses mediated by one, two, or three immunodominant T cell clones are
removed. The following cases are considered:
(a)
Control: No T cells are removed. Clones 1-5 all respond.
(b)
SKO: clone 1 is removed. Only clones 2-5 respond.
(c)
DKO: clones 1 and 2 are removed. Only clones 3-5 respond.
(d)
TKO: clones 1-3 are removed. Only clones 4 and 5 respond.
Figure
6
shows the numerical simulations obtained in all four cases. As expected,
we see in Fig.
6
a that the five T cell clones fall into a hierarchy based on their
reactivities. When the dominant clone is removed (a case shown in Fig.
6
b),
the second most reactive clone partially compensates, i.e., whereas the peak of
the response from clone 2 is 44.85 in the control experiment, it rises to 62.39 in
the SKO experiment. Similarly, when the two most dominant clones are removed
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