CHAPTER 7
The Development of T Lymphocytes
Questions
7–1
After interaction with thymic stromal cells, _____, a glycoprotein not expressed by the
uncommitted progenitor cell is activated in developing thymocytes. (Select all that
apply.)
a. CD2
b. CD34
c. CD5
d. CD127 (IL-7 receptor)
e. CD44.
7–2
_____ is a T-cell-specific adhesion molecule expressed before the expression of a
functional T-cell receptor while the thymocytes are still in their double-negative stage of
development.
a. CD4
b. CD8
c. CD25
d. CD2
e. CD3.
7–3
Which of the following cell-surface glycoproteins is characteristic of stem cells, but stops
being expressed when a cell has committed to the T-cell developmental pathway?
a. CD2
b. CD3
c. CD25
d. CD34
e. MHC class II.
7–4
Which of the following statements about Notch 1 is correct? (Select all that apply.)
a. Notch 1 is expressed on thymic epithelial cells.
b. In the absence of Notch 1 expression, T cells can complete their differentiation.
c. Notch 1 is to T-cell development as Pax-5 is to B-cell development.
d. Notch 1 contains two distinct domains, one of which is proteolytically cleaved
and becomes a transcription factor in the nucleus.
2
e. The extracellular domain of Notch 1 must interact with a ligand on thymic
epithelium to initiate cleavage and separation of the Notch 1 extracellular and
intracellular domains.
7–5
Which of the following is the first stage of T-cell receptor gene rearrangement in : T
cells?
a. V → D
b. D → J
c. V → D
d. D → J
e. V → J.
7–6
Which of the following statements about the successive rearrangement of : T-cell
receptors is correct? (Select all that apply.)
a. Unproductive rearrangement to the C1 locus can be rescued by a second
rearrangement to the C2 locus.
b. Unproductive rearrangement to the C2 locus can be rescued by a second
rearrangement to the C1 locus.
c. Unproductive rearrangements between V and J can be rescued by a second
rearrangement between upstream V and downstream J segments.
d. When the chain undergoes a successive gene rearrangement, the unproductive
intervening rearranged gene segments are deleted.
e. The -chain locus is permanently deleted as an extrachromosomal circle when the
-chain gene rearranges.
7–7
Which of the following is the first T-cell receptor complex containing the chain to
reach the cell surface during the development of T lymphocytes?
a. ::CD3
b. :CD3
c. ::CD3
d. :CD44
e. pT::CD3.
7–8
The T-cell receptor -chain locus can undergo successive gene rearrangements to rescue
unproductive V(D)J rearrangements.
A. What aspects of gene segment rearrangement at the TCR locus make this
possible?
B. Can the immunoglobulin heavy-chain locus, which is also composed of V, D, and
J segments, undergo successive rearrangements? If not, give the reasons for the
difference.
3
7–9
Indicate which of the following statements is true (T) or false (F).
a. __ Immature T cells failing to successfully recombine a -chain locus die by
apoptosis.
b. __ Apoptotic T cells are ingested by medullary epithelial cells.
c. __ Allelic exclusion of the T-cell receptor and chains is effective; therefore,
all T cells express only one T-cell receptor on the cell surface.
d. __ T-cell receptor rearrangements have many features in common with
immunoglobulin rearrangement, including the use of the RAG-1 and RAG-2
genes.
e. __ The expression of the pre-T-cell receptor is required in order to halt -, -, and
-chain rearrangements.
7–10
Once a thymocyte has productively rearranged a -chain gene, which of these event(s)
can occur subsequently? (Select all that apply.)
a. binds to pT and is expressed on the cell surface with the CD3 complex and
chain.
b. Rearrangement of -, -, and -chain genes ceases as a result of the suppression of
expression of RAG-1 and RAG-2.
c. The pre-T cell proliferates and produces a clone of cells all expressing an
identical chain.
d. Expression of CD34 and CD2 gives rise to double-positive thymocytes.
e. -, -, and -chain loci rearrange simultaneously.
7–11
_______ of thymocytes is necessary to produce a T-cell repertoire capable of interacting
with self-MHC molecules.
a. Positive selection
b. Negative selection
c. Apoptosis
d. Receptor editing
e. Isotype switching.
7–12
Which of the following statements are true of a T cell that expresses two chains (and
thus two different T-cell receptors) as a result of ineffective allelic exclusion of the
chain during rearrangement? (Select all that apply.)
a. Engaging either of the T-cell receptors on MHC molecules of the thymic
epithelium will result in positive selection.
b. One of the T-cell receptors will be functional while the other will most probably
be non-functional.
c. If either T-cell receptor binds strongly to self-peptides presented by self-MHC
molecules, the thymocyte will be negatively selected.
d. One of the T-cell receptors may be autoreactive but escape negative selection
because its peptide antigen is present in tissues other than the thymus.
4
e. Subsequent gene rearrangements may give rise to a : T-cell receptor.
7–13
Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) is
caused by a defect in
a. cathepsin L
b. a transcription factor called AIRE that regulates tissue-specific gene expression in
the thymus
c. the production of regulatory CD4 T cells
d. FoxP3
e. T-cell receptor gene rearrangement.
7–14
A feature of T-cell development that may contribute to tumor development is
a. positive selection
b. negative selection
c. apoptosis
d. DNA rearrangement
e. expression of two chains by the same T cell.
7–15
Which of the following is mismatched?
a. double-negative CD3– thymocytes: cortico-medullary junction
b. double-negative CD3– thymocytes: subcapsular zone
c. double-positive CD3+ thymocytes: cortico-medullary junction
d. cortical epithelial cells: subcapsular regions
e. dendritic cells: cortico-medullary junction.
7–16
The human thymus begins to degenerate as early as one year after birth. This process is
called ______ and is marked by the accumulation of ___ once occupied by thymocytes.
a. thymectomy; dendritic cells
b. involution; fat
c. differentiation;: T cells
d. negative selection; : T cells
e. involution; thymic stroma.
7–17
Discuss why there are T-cell tumors corresponding to early and late T-cell developmental
stages but not to intermediate stages.
7–18
A. Explain how Southern blotting could be used to identify a T-cell tumor expressing
a rearranged T-cell receptor gene.
5
B. What result would you expect when comparing DNA extracted from (i)
spermatocytes, (ii) normal peripheral blood mononuclear cells (PBMCs), and (iii)
PBMCs of a patient with T-cell leukemia?
6
Answers
7