Lymphocyte Development Flashcards
What do TCRs bind to?
- Antigen-derived peptide
- peptide bound to MHC class
Describe the structure of the TCR.
- regions
- disulfide bonds
- transmembrane domain
- recombination chains
α chain = VJ
β = VDJ
How do T-cells express unique antigen receptors?
VDJ/VJ recombination
Cells entering the thymus are (_____) to becoming a lymphocyte and express antigen-specific receptors.
A. not committed
B. naive/mature
C. B cells
A. not committed
T/F. Cells leaving the thymus are naive/mature T-cells and express specific antigen TCRs.
True
T-cells development occurs in the:
thymus
Describe the migration of T-cell development.
- precursor T-cells develop in the bone marrow
- Immature T-cells migrate from bone marrow through the blood into the thymus
- Immature T-cells travel through the thymus at the cortex
- T-cells that undergo selection migrate to the medulla
List the stages the T-cells undergo in the thymus.
- Double negative (DN): do not express CD4 or CD8
- Double positive (DP): express both CD4 and CD8
- Single positive: expresses either CD4 or CD8
In which stage does the recombination of the TCR gene segments (VDJ/VJ) occur?
DN stages
What are the two stages T-cell development occurs?
- Early thymocyte development
- commit to T-cell lineage
- Initiate V(D)J recombiation
- expand cells - T cell maturation
- positive selection
- negative selection
- lineage commitment
When thymocytes arrive at the thymus, what early cells do they have the possibility of becoming?
- NK cells
- dendritic cells
- B cells
T/F. When cells arrive at the thymus they are T-cells.
False. When cells arrive at the thymus they aren’t technically T-cells.
T cell lineage commitment occurs due to signals received by the progenitor cell from thymic epithelial cells. Name that signaling receptor.
Notch
If the cell has Notch+ or Notch- which cell lineage are they committed to?
Notch+: T cells
Notch-: B cells
When thymocytes progress to the DN stages what essentially occurs?
- gets TCR α and β
- cells will test β chain via β selection = proliferation
- initiates α chain rearrangement and selection
- VDJ rearrangement is stopped once selection occurs
- enters DP stage
After β selection, what stage do the thymocytes enter?
DP
What occurs in the DP stage?
- functional TCR
- cell expresses both CD4 AND CD8 (CD4+, CD8+)
- undergoes positive and negative selection
Describe positive and negative selection of thymic cells.
- positive selection: selects thymocytes receptors capable of binding self-MHC molecules with low affinity
- MHC restriction - negative selection: selects against thymocytes receptors with high affinity for self-MHC/peptide complexes
- self tolerance
MHCI is present on …
all nucleated cells
- T cells
- B cells
- macrophages
- dendritic cells
- epithelial cells of the thymus
MHCII is present in …..
APCs
- B cells
- macrophages
- dendritic cells
- epithelial cells of the thymus
The function of cortical thymic epithelial cells (cTEC)?
express high levels of MHC class I and II
- mediate positive selection
Double positive thymocytes learn (____) in the thymus.
MHC restriction
What are the 3 possible outcomes when T cells encounter self-peptide/MHC?
- TCRs can’t bind = death by neglect
- TCRs bind too strongly (high affinity) = apoptosis
- TCRs bind just right (low affinity) = positive selection
- recognizes and interacts with self peptide
- ensures MHC restriction
- becomes CD4 or CD8, single positive
Negative selection ensures….
self tolerance (central tolerance)
