Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

CHAPTER 24 END-OF-CHAPTER PROBLEMS
1341
Why do not all viral peptides sensitize the target cells for
lysis by the cytotoxic T cells?
B. It is thought the MHC molecules come to the cell
surface with peptides already bound. If that is so, how do
you imagine that these experiments worked?
24–8 Working out the rules by which T cells interact
with their target cells was complicated. Some of the key
observations came from studying the way cytotoxic T cells
killed cells infected with choriomeningitis virus (LCMV).
Cytotoxic T cells derived from mice expressing “k-type”
class I MHC proteins lysed LCMV-infected cells expressing
the same k-type MHC protein, but they did not lyse
infected cells from mice expressing “d-type” class I MHC
proteins (Figure Q24–2). Similarly, cytotoxic T cells from
d-type mice lysed infected d-type cells, but not infected
k-type cells. LCMV can kill both k-type and d-type mice.
LCMV
k-type mouse
cytotoxic
T cells
added to
LCMV infected
k-type mouse
fibroblasts
d-type mouse
fibroblasts
T cells kill
target cells
Figure Q24–2 Pattern of killing of LCMV-infected fibroblasts by
cytotoxic T cells from an LCMV-infected k-type mouse (Problem 24–8).
A. If homozygous d-type mice were bred to homozygous
k-type mice to generate d-type/k-type heterozygous
progeny, would you expect that cytotoxic T cells from these
heterozygotes, when infected with LCMV, to be able to lyse
infected d-type cells? How about infected k-type cells?
Explain your answers.
B. Oddly enough, LCMV infection does not kill mice
that lack a thymus—such as “nude” mice, so called because
they also lack hair. If a thymus is transplanted back into a
nude mouse, it will die when infected with LCMV. Suppose
that a d-type/k-type heterozygous nude mouse was given
a thymus from an d-type donor. Would you expect its cytotoxic
T cells to be able to lyse infected d-type cells? How
about infected k-type cells? Explain your answers.
24–9 Before exposure to a foreign antigen, T cells with
receptors specific for the antigen are a tiny fraction of the T
cells—on the order of 1 in 10 5 or 1 in 10 6 T cells. After exposure
to the antigen, only a small number of dendritic cells
Figure Q24-6
typically display the antigen on their surface. How long
does it take for such antigen-presenting dendritic cells to
interact Adapted with the from antigen-specific MBoC5 24.58/24.56 T cells, which is the key
first step in T cell activation and clonal expansion? The
dynamics of the search process were examined by labeling
dendritic cells red and T cells green, so that contacts in an
intact lymph node could be scored visually using two-photon
fluorescence microscopy (Figure Q24–3A). The frequency
of contacts between dendritic cells and T cells
from such experiments is given in Figure 24–3B. Assuming
that 100 dendritic cells present the specific antigen, how
long would it take them to scan 10 5 T cells? How long for
10 6 T cells?
YES
NO
(A)
(B)
encounters
1
1
1
3
* * *
2 2
3
0:35 1:20 2:30
600
400
200
0
0 10 20 30 40 50 60
minutes
Figure Q24–3 Scanning
of the T cell repertoire by
dendritic cells (Problem 24–9).
(A) Contacts between different
T cells and one dendritic
cell. T cells are green and
dendritic cells are red. The
dendritic cell labeled with
an asterisk contacts a total
of three T cells (numbered)
over time in this sequence
of images. Times are shown
as hours: minutes. (B) Plot of
T cell contacts for individual
dendritic cells over time.
(A, from P Bousso and
E. Robey, Nat. Immunol.
4:579–581, 2003. With
permission from Macmillan
Publishers Ltd.)
24–10 At first glance, it would seem a dangerous strategy
for the thymus to actively promote the survival, maturation,
and emigration of developing T cells that bind weakly
to self peptides bound to self MHC molecules. Would it
not be safer to get rid of these T cells, along with those that
bind Problems strongly to such 25.201/Q24.04
self-peptide–MHC complexes, as this
would seem a more secure way to avoid autoimmune reactions?
24–11 CD4 proteins on helper and regulatory T cells
serve as co-receptors that bind to invariant parts of class
II MHC proteins. CD4 is thought to increase the adhesion
between T cells and antigen-presenting cells (APCs) that
are initially connected only weakly by the T cell receptor
bound to its specific peptide–MHC complex. To test this
possibility, you label cell-surface MHC molecules with a
fluorescently labeled peptide so that you can detect individual
peptide–MHC complexes at the interface between
the APCs and the T cells in a culture dish. To detect T cell
responses—the sign of a productive contact—you load
them with a Ca 2+ indicator dye, as cytosolic Ca 2+ increases
when lymphocytes are active. You now count the peptide–
MHC complexes at a large number of interfaces (immunological
synapses) and measure the resulting uptake of Ca 2+
in the adherent T cells (Figure Q24–4, red circles). When
you repeat the experiment in the presence of blocking antibodies
against CD4, you get a different result (blue circles).
Do these results support or refute the notion that CD4 augments
T cell receptor binding? Explain your answer.
Figure Q24–4 Role of
CD4 in the T cell response
(Problem 24–11). The uptake
of Ca 2+ in cells with different
numbers of fluorescently
40
labeled peptide–MHC
complexes at the interface
30
between the T cells and the
antigen-presenting cells.
20
The results in the absence
of CD4-blocking antibodies
10
are shown by the red curve;
results in the presence of
0
0 20 40 60 80 CD4 antibodies are shown
number of peptide–MHC complexes by the blue curve.
calcium uptake