IMM: BLOCK 2: LECTURE 6: T-CELL DEVELOPMENT

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Questions and Answers

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?

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?

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?

They shut down their recombination machinery. Signup and view all the answers

What characterizes the cell once the γδ T-cell receptor appears on the cell surface?

It leaves the thymus to travel in blood to other tissues. Signup and view all the answers

What is the initial condition of T-cell precursors entering the thymus?

They express the HSC marker CD34. Signup and view all the answers

What is the primary purpose of positive selection in T-cell development?

To ensure T cells can recognize foreign antigens presented by MHC molecules Signup and view all the answers

What role does the Notch1 receptor play in T-cell development?

It induces transcription factors essential for maturation. Signup and view all the answers

During T-cell development, which protein is primarily involved in signaling pathways that influence hematopoietic stem cells?

Notch Signup and view all the answers

Which surface markers indicate a double-negative (DN) thymocyte progenitor?

CD34 but no mature T cell markers. Signup and view all the answers

Which of the following statements accurately describes the differences between αβ TCR and γδ TCR?

Only γδ TCR has two constant segments. Signup and view all the answers

What is a consequence of the absence of Notch1 in T-cell development?

Complete failure of T-cell maturation. Signup and view all the answers

What happens after Notch1 binds to its ligand on thymic epithelium?

It cleaves intracellular domains releasing transcription factors. Signup and view all the answers

What relationship exists between negative selection and central tolerance?

Negative selection helps maintain central tolerance by eliminating self-reactive T cells. Signup and view all the answers

Which proteins undergo change during the commitment to the T-cell lineage?

CD2, CD5, and other cell-surface proteins. Signup and view all the answers

Which change occurs during the development of T cells in regard to CD4 and CD8 expression?

T cells start as double-negative, then become double-positive before maturing. Signup and view all the answers

Which of the following is true regarding the development of αβ and γδ T cells?

They arise from a common double-negative thymocyte progenitor. Signup and view all the answers

What is the role of the microenvironments within the thymus during T-cell development?

They support different stages of T-cell maturation and selection processes. Signup and view all the answers

What is the first step in the T-cell commitment process?

Expression of various cell-surface and intracellular proteins. Signup and view all the answers

How does the expression of TCR develop in T cells?

TCR develops progressively, starting from double-negative stages to double-positive states. Signup and view all the answers

Which of the following accurately compares δγ T cells with B1 and B2 cells?

δγ T cells differ in organization from both B1 and B2 cells. Signup and view all the answers

What role do RAG proteins play in T-cell development?

They are essential for gene rearrangement. Signup and view all the answers

Which protein is responsible for inserting N nucleotides during somatic recombination?

TdT Signup and view all the answers

What signal is critical for the pre-T-cell receptor's successful formation?

Presence of CD4, CD8, and CD3 complex Signup and view all the answers

What is the consequence of successful assembly of a pre-T-cell receptor?

The cell initiates division and clonal expansion. Signup and view all the answers

What is the function of Th-Pok during T-cell development?

It aids in the development of single-positive CD4 T cells. Signup and view all the answers

What is the primary outcome when a productive α-chain gene rearrangement occurs in T cells?

The T cell assembles an αβ receptor and commits to the αβ lineage Signup and view all the answers

In double-negative thymocytes, which gene rearrangements can occur concurrently?

β, γ, and δ genes rearrange Signup and view all the answers

What triggers the differentiation of a double-negative thymocyte into a mature γδ T cell?

Functional rearrangement of both γ and δ-chain genes Signup and view all the answers

What occurs if a successful β-chain gene rearrangement is made before γ and δ genes have been rearranged?

The pre-T-cell receptor is formed and signals for the cell to proliferate Signup and view all the answers

Which cells are primarily produced following the rearrangement of the α-chain gene in T cells?

Mature αβ T cells Signup and view all the answers

What happens to a double-negative thymocyte that fails to productively rearrange its α-chain gene?

The cell cannot express CD4 or CD8 Signup and view all the answers

What is formed when the γ and δ chain genes rearrange successfully first in a double-negative thymocyte?

A γδ receptor Signup and view all the answers

What initiates the recombination process in pre-T cells?

Assembly of a pre-T-cell receptor Signup and view all the answers

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.