Podcast
Questions and Answers
What is the consequence of a productive rearrangement of both γ- and δ-chain genes?
What is the consequence of a productive rearrangement of both γ- and δ-chain genes?
- The cell remains a double-negative T-cell.
- The cell becomes a memory T-cell.
- The cell commits to the γδ T-cell lineage. (correct)
- The cell commits to the αβ T-cell lineage.
What happens to the recombination machinery after the rearrangement of a β-chain gene?
What happens to the recombination machinery after the rearrangement of a β-chain gene?
- It remains unaffected and continues to rearrange other genes.
- It begins to rearrange δ- and γ-chain genes.
- It becomes more efficient in producing T-cell receptors.
- It is shut down. (correct)
What occurs when the β-chain is successfully tested for quality?
What occurs when the β-chain is successfully tested for quality?
- The cell undergoes further rearrangements of the δ-chain.
- The cell exits the thymus immediately.
- The cell proliferates to form a clone of β-chain positive cells. (correct)
- The cell is marked for apoptosis.
What is the initial fate of cells that already have rearranged a γ- or a δ-chain gene?
What is the initial fate of cells that already have rearranged a γ- or a δ-chain gene?
What characterizes the cell once the γδ T-cell receptor appears on the cell surface?
What characterizes the cell once the γδ T-cell receptor appears on the cell surface?
What is the initial condition of T-cell precursors entering the thymus?
What is the initial condition of T-cell precursors entering the thymus?
What is the primary purpose of positive selection in T-cell development?
What is the primary purpose of positive selection in T-cell development?
What role does the Notch1 receptor play in T-cell development?
What role does the Notch1 receptor play in T-cell development?
During T-cell development, which protein is primarily involved in signaling pathways that influence hematopoietic stem cells?
During T-cell development, which protein is primarily involved in signaling pathways that influence hematopoietic stem cells?
Which surface markers indicate a double-negative (DN) thymocyte progenitor?
Which surface markers indicate a double-negative (DN) thymocyte progenitor?
Which of the following statements accurately describes the differences between αβ TCR and γδ TCR?
Which of the following statements accurately describes the differences between αβ TCR and γδ TCR?
What is a consequence of the absence of Notch1 in T-cell development?
What is a consequence of the absence of Notch1 in T-cell development?
What happens after Notch1 binds to its ligand on thymic epithelium?
What happens after Notch1 binds to its ligand on thymic epithelium?
What relationship exists between negative selection and central tolerance?
What relationship exists between negative selection and central tolerance?
Which proteins undergo change during the commitment to the T-cell lineage?
Which proteins undergo change during the commitment to the T-cell lineage?
Which change occurs during the development of T cells in regard to CD4 and CD8 expression?
Which change occurs during the development of T cells in regard to CD4 and CD8 expression?
Which of the following is true regarding the development of αβ and γδ T cells?
Which of the following is true regarding the development of αβ and γδ T cells?
What is the role of the microenvironments within the thymus during T-cell development?
What is the role of the microenvironments within the thymus during T-cell development?
What is the first step in the T-cell commitment process?
What is the first step in the T-cell commitment process?
How does the expression of TCR develop in T cells?
How does the expression of TCR develop in T cells?
Which of the following accurately compares δγ T cells with B1 and B2 cells?
Which of the following accurately compares δγ T cells with B1 and B2 cells?
What role do RAG proteins play in T-cell development?
What role do RAG proteins play in T-cell development?
Which protein is responsible for inserting N nucleotides during somatic recombination?
Which protein is responsible for inserting N nucleotides during somatic recombination?
What signal is critical for the pre-T-cell receptor's successful formation?
What signal is critical for the pre-T-cell receptor's successful formation?
What is the consequence of successful assembly of a pre-T-cell receptor?
What is the consequence of successful assembly of a pre-T-cell receptor?
What is the function of Th-Pok during T-cell development?
What is the function of Th-Pok during T-cell development?
What is the primary outcome when a productive α-chain gene rearrangement occurs in T cells?
What is the primary outcome when a productive α-chain gene rearrangement occurs in T cells?
In double-negative thymocytes, which gene rearrangements can occur concurrently?
In double-negative thymocytes, which gene rearrangements can occur concurrently?
What triggers the differentiation of a double-negative thymocyte into a mature γδ T cell?
What triggers the differentiation of a double-negative thymocyte into a mature γδ T cell?
What occurs if a successful β-chain gene rearrangement is made before γ and δ genes have been rearranged?
What occurs if a successful β-chain gene rearrangement is made before γ and δ genes have been rearranged?
Which cells are primarily produced following the rearrangement of the α-chain gene in T cells?
Which cells are primarily produced following the rearrangement of the α-chain gene in T cells?
What happens to a double-negative thymocyte that fails to productively rearrange its α-chain gene?
What happens to a double-negative thymocyte that fails to productively rearrange its α-chain gene?
What is formed when the γ and δ chain genes rearrange successfully first in a double-negative thymocyte?
What is formed when the γ and δ chain genes rearrange successfully first in a double-negative thymocyte?
What initiates the recombination process in pre-T cells?
What initiates the recombination process in pre-T cells?
Study Notes
T Cell Development
- T cell development begins with a hematopoietic stem cell
- Key receptors involved in T cell development include Notch1 and its ligand
- Notch1 signaling initiates T cell development by cleaving its intracellular domain and translocating it to the nucleus
- Notch1 signaling initiates gene expression essential for T cell development
- Both αβ and γδ T cells develop from a common double-negative T cell progenitor (DN)
- DN progenitors express the HSC marker CD34, but not markers of mature T cells
- The two lineages of T cells (αβ and γδ) are distinguished by the rearrangement of their T cell receptor genes.
- Cells that productively rearrange both a γ- & δ-chain gene commit to γδ T cell lineage.
- Cells that productively rearrange a β-chain gene shut down recombination machinery and may rearrange a γ- or δ-chain gene.
- When rearrangement of the β-chain gene occurs before γ & δ genes, a pre-T-cell receptor assembles and signals cell to become a pre-T cell.
- Pre-T cells express CD4 and CD8 markers.
- Pre-T cell receptor function is tested by a signaling pathway depending on the presence of CD4, CD8, CD3 signaling complex, and tyrosine kinases ZAP70 & Lck.
- CD2, an adhesion molecule on T cells, interacts with CD58 on other cells.
- Th-Pok, a transcription factor, is expressed late in development and is necessary for single-positive CD4 T cells to develop from double-positive thymocytes
T Cell Receptor Rearrangement
- αβ TCR composition: Chromosome 14 (α chain) with V and J segments, and one constant segment; Chromosome 7 (β chain) with V, D, & J segments & two potential constant segments
- γδ TCR composition: Chromosome 7 (γ chain) with V and J segments, and two constant segments; Chromosome 14 (δ chain) with V, D, & J segments and one constant segment
- Successful β-chain rearrangement leads to pre-T-cell receptor formation.
- The pre-T-cell receptor is composed of a β chain and a pTα chain.
Role of RAG Proteins
- RAG proteins are essential for gene rearrangement.
- RAG proteins are selectively expressed during β and α gene rearrangements.
Other Enzymes
- TdT- inserts N nucleotides
- pTα- a defining component of the pre-T cell receptor
- ZAP70- zeta chain–associated protein kinase 70, a tyrosine kinase
- Lck- a tyrosine kinase
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Description
Explore the complex process of T cell development that begins with hematopoietic stem cells and involves crucial signaling pathways, specifically Notch1. This quiz delves into the differentiation of αβ and γδ T cells from common progenitors, including the role of T cell receptor gene rearrangement in lineage determination.
