BIOL 435 Ch. 8 p.1 (T-Cell Development)

Question 1

TCR structure

Answer 1

• variable and constant regions
• always membrane bound
• beta or delta chains = BCR H-chain
• alpha or gamma chains = BCR L-chains

Question 2

TCR protein structure

Answer 2

• used monoclonal Ab to bond to specific parts of TCR to purify them
• heterodimer with an alpha and beta chain

Question 3

early thmocyte development

Answer 3

-when first arrive, they aren’t T-cells
>can become NK cells, dendritic cells, B-cells and myeloid cells
*Notch (a receptor) commits them to the T-lineage
>GATA-3 TF becomes activated

Question 4

steps in thymus

Answer 4

1. Enter at CMJ: thymic settling precursors, DN1
2. Cortex: DN2 (may become gamma-delta_
   >*commitment to T-lineage
3. Subscapular cortex: DN3, rearrangment
4. Cortex: DN4, alphabeta TCR DP, cell death or
5. Through CMJ into medulla: CD4+ SP or CD8+ SP

Question 5

DN2

Answer 5

-starts rearrangement
>beta, delta, gamma
*need both delta and gamma to be successful
*only need beta successful=more often

Question 6

DN1 and DN2

Answer 6

-are mulipotent

>can give rise to myeloid and NK cells

Question 7

T-cells that survive selection in thymus cortex

Answer 7

-migrate into medulla

Question 8

+/- selection stages

Answer 8

-for a cell to become SP CD4+ or SP CD8+

Question 9

if gamma delta succesful

Answer 9

-can leave the thymus
-0.5% of T-cells
-can secrete cytokines without Ag
-recognize lipids with unconventional MHC
*1st line of defense
>mucosa and skin

Question 10

allelic exclusion

Answer 10

• not absolute

- may get 2 alpha chains

Question 11

final screening in thymus

Answer 11

• removes autoreactive cells

- release into peripheral bloodstream

Question 12

TCR rearrangement begins

Answer 12

-in the cortex and DN2 stage

Question 13

stages of T-cell development

Answer 13

1. CLPs leave bone marrow and enter thymus
2. DN
3. Gamma, beta, delta rearrangements occur simultaneously
4. Display with pre-T-alpha=shuts down
5. End of DN, pre-TCR expresses CD4 and CD8=DP

Question 14

TCRbeta rearrangement

Answer 14

• 3x as likely

- first to take place and succeed

Question 15

TCR gamma delta

Answer 15

-more common in fetal development
>environment may provide different signal cues
-most capable of secreting cytokines upon release from thymus
-less diverse
-1st response to pathogens and respond to cellular stress

Question 16

TCR genes and rearrangement

Answer 16

-similar to Ig genes
-specific RSS
>some with 2D delta (12/23 rule)
>2D beta possible, but not observed
*D has a 12 and 23 on ‘either side’

Question 17

if delta gamma successful

Answer 17

-TCR is tested and DN T-cell is release from thymus

Question 18

if beta rearranges

Answer 18

• tested with a pre-Talpha (+ and - selection)

- if okay=alpha-chain rearrangment starts

Question 19

CD3

Answer 19

• part of TCR complex

- has ITAMs

Question 20

beta-selection

Answer 20

• DN thymocytes undergo it
• results in proliferation/differentiation
• than get DP

Question 21

DP stage

Answer 21

• functional TCR alpha chain replaces surrogate

- positive/negative selection yields mature SP T-cell

Question 22

CD4, CD8 DP thymocytes

Answer 22

-make up 80% of thymic cells
-undergo thymic selection
>in the cortex

Question 23

postive selection

Answer 23

• selects thymocyes bearing receptors capable of binding self-MHC with low affinity=MHC restriction
• 2-5%

Question 24

Death by neglect

Answer 24

• fail positive selection and fail to receive needed survivial signals
• 90-96%
• die by apoptosis

Question 25

cTEC

Answer 25

• cortex thymic epithelial cells
• expres high leveles of MHC1 and MHC2 molecules
• developing T-cells ‘browse’ possible self peptide/MHC complexes

Question 26

3 outcomes when encounter cTEC

Answer 26

1. TCR can’t bind-die by neglect
2. TCR binds too strong-negative selection
3. TCR binds just right-positive selection (SP stage occurs)