Ch 9: T-cell development

Question 1

Early stage of Thymocyte cell developmet

Answer 1

T-cell receptor independent and brings cells
through uncommitted CD4CD8 (double negative,
DN) stages to the T-cell receptor-expressing,
CD4CD8 (double positive, DP) stage. The specific
events in this early stage include:
1. commitment of hematopoietic precursors to the T cell
lineage,
2. the initiation of antigen receptor gene rearrangements, and
3. the selection and expansion of cells that have successfully rearranged one of their T-cell receptor genes
(-selection).

Question 2

Th e second phase of T-cell development

Answer 2

dependent on T-cell receptor interactions and brings cells
to maturity from the CD4CD8 stage to the CD4 or
CD8 single positive (SP) stage. Th e events in this last
phase of development include:

Postive selection

Negative selection

Lineage commitment

Question 3

lineage commitment

Answer 3

commitment of thymocytes to
effector cell lineages, including CD4 helper or CD8
cytotoxic populations.

Question 4

which stage in T cell development commits the cell to a specific lineage

Answer 4

precursor only becomes fully committed to the T-cell lineage
in the late DN2 stage of T-cell development

Notch is super important for this

Question 5

GATA-3

Answer 5

transcription factor GATA-3 is a critical participant in Notch-mediated T-cell
commitment

Question 6

DN1 thymocytes

Answer 6

the fi rst to enter the thymus and
are still capable of giving rise to multiple cell types. Th ey
express only c-kit and CD44 (c-kitCD44CD25), but
once they encounter the thymic environment and become
resident in the cortex, they proliferate and express CD25,
becoming DN2 thymocytes

Question 7

DN2 thymocytes

Answer 7

(c-kitCD44CD25).
During this critical stage of development, the genes for
the TCR g, d and b chains begin to rearrange; however, the
TCR a locus does not rearrange, presumably because the
region of DNA encoding TCRa genes is not yet accessible to
the recombinase machinery. At the late DN2 stage, T-cell
precursors fully commit to the T-cell lineage and reduce
expression of both c-kit and CD44

Question 8

DN3

Answer 8

(c-kitCD44CD25) stages continue rearrangement of the TCg, TCRd, and TCRb
chains and make the fi rst major decision in T-cell development: whether to join the TCRgd or TCRab T-cell lineage. Those DN3 T cells that successfully rearrange their
b chain and therefore commit to the TCRab T-cell lineage
lose expression of CD25, halt proliferation, and enter the
fi nal phase of their DN stage of development

Question 9

DN4

Answer 9

(c-kitlow/CD44CD25), which mature directly into

CD4CD8 DP thymocytes

Question 10

TCRgd cells

Answer 10

play
an important role, particularly in protecting our mucosal
tissues from outside infection

Question 11

In what phase does VDJ rearrangement occur

Answer 11

DN2

Question 12

Mature TCRgd T cells

Answer 12

Most do not
go through the DP stage of thymocyte development and
leave the thymus as mature DN T cells. Many emerge from
the thymus with the ability to secrete cytokines, a capacity
gained by most TCRab cells only aft er they encounter
antigen in secondary lymphoid tissues.

Question 13

Pre-TCR signaling

Answer 13

1. Maturation to the DN4 stage (c-kitlow/CD44CD25)
2. Rapid proliferation in the subcapsular cortex
3. Suppression of further rearrangement of TCR b-chain
   genes, resulting in allelic exclusion of the b-chain
   locus
4. Development to the CD4CD8 double-positive (DP)
   stage
5. Cessation of proliferation
6. Initiation of TCRa chain rearrangement

Question 14

b-selection

Answer 14

the process in which DN thymocytes that have succesfully arranged their TCRb chains are identified and expanded

preTa chain acts as a surrogate for the real TCRa chain (which has not rearranged yet) and assembles with the successfully rearranged b chain and the CD3 complex

=the preTCR complex
=> inhibits the signal transduction pathway??

Question 15

Why are T cell a chains rearranged after b chains

Answer 15

it is important to note that the proliferative phase prior to
a chain rearrangement enhances receptor diversity considerably by generating clones of cells with the same TCR
b-chain rearrangement. Each of the cells within a clone can
then rearrange a diff erent a-chain gene, thereby generating
an even more diverse population than if the original cell had
undergone rearrangement at both the b- and a-chain loci
prior to proliferation

Question 16

allelic exclusion

Answer 16

Most T cells fully rearrange and express a TCRb chain
from only one of their two TCR alleles,

Allelic exclusion is the result of
inhibition of further rearrangement at the other TCRb
allele (which must be fully rearranged to be expressed).
Th is can be accomplished by reducing RAG expression so
no more rearrangement can occur, as well as by making the
locus inaccessible to further RAG interaction via more
permanent changes in chromatin packaging

Question 17

Clonal deletion

Answer 17

high-affi nity TCR interactions directly induce apoptotic signals.
Clonal deletion of DP thymocytes appears to be optimally
mediated by the same cells (APCs) and same interactions
(high-affi nity TCR engagement coupled with costimulatory
signals) that activate mature T cells.