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Printable Handouts
Navigable Slide Index
- Introduction
- RAG induction and V(D)J recombination
- Somatic recombination of TCR genes
- Two TCR-based lineages: αβ and γδ T cells
- Decision #2: αβ or γδ T cell?
- Studying T cell development with mouse models
- T cell subset selection in the mouse thymus
- Surrogate pTα and the pre-TCR
- Downstream signalling from pre-TCR to the nucleus
- Signal strength model for αβ/γδ lineage commitment (1)
- Signal strength model for αβ/γδ lineage commitment (2)
- Notch and the pre-TCR dictate the fate of T cells
- Critical role of the pre-TCR in αβ T cell development
- Major checkpoints in αβ T cell development
- Selection of thymocytes on MHC & self peptide
- Decision #3: CD4+ or CD8+ αβ T cell? (1)
- Decision #3: CD4+ or CD8+ αβ T cell? (2)
- Duration of signal determines αβ T cell type
- Overview of T cell development so far
- Decision #4: Tconv or Treg CD4+ αβ T cell?
- TCR signal strength
- Decision #5: γδIFN or γδ17 T cell?
- Developmental pre-programming of γδ T cells
- TCR signal strength models for αβ and γδ T cells
- γδ T cell subsets in the tumour microenvironment
- Acknowledgements
- Summary
Topics Covered
- Somatic recombination of TCR genes
- αβ and γδ T cell differentiation
- The pre-TCR
- CD4+ or CD8+ αβ T cell lineage?
- Determinants of Tconv or Treg T cell development
- γδIFN or γδ17 T cell development?
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Talk Citation
Silva-Santos, B. (2021, December 26). Lineage decisions in the thymus: αβ and γδ T cell lineages [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 7, 2024, from https://doi.org/10.69645/BQQA2576.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Bruno Silva-Santos has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Lineage decisions in the thymus: αβ and γδ T cell lineages
Published on December 26, 2021
35 min
Other Talks in the Series: The Immune System - Key Concepts and Questions
Transcript
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0:03
After IL-7 and IL-7 receptor provide the survival signals to early pro-T-cells,
the major event in T-cell development occurs,
which is the rearrangement of the T-cell receptor genes.
The T-cell receptor characterizes T-cells, this is what's different between a T-cell
and the other lineages of immune cells, so the rearrangement of the T-cell
receptor genes, and the expression of the T-cell receptor,
is the key event that will take place in the thymus.
This is dependent on a key enzyme called RAG, recombination activating
gene, is the enzyme that orchestrates the rearrangement of the T-cell receptor
genes, so once again, children that have mutations in RAG will have another type
of SCID (severe combined immunodeficiency).
In this case it's called Omenn syndrome, after the person who identified it,
and it means the absence of both T- and B-cells.
In contrast with X-linked SCID described in the previous slide - where T-cells were
absent but B-cells were there - in this case, because RAG is not expressed,
and RAG is required for both B- and T-cell development, the child will be devoid
of both B- and T-cells.
This will result in an even more aggressive immunodeficiency.
In this case, once again, bone marrow transplantation will be required, so that
the child can develop normal B- and T-cells, once it gets healthy bone marrow
with healthy T- and B-cell progenitors that can express the RAG protein.
What does RAG do?