KARA - Immunology Exam 4 - Chapter 7 & 8.docx

And leads to expression of cd4 and cd8 receptor most

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and leads to expression of CD4 and CD8  Receptor most abundant type found on T cells. TCR -chain locus = variable (V), diversity (D) and joining (J) gene segments and is rearranged first (similar to heavy chain in Ig’s) TCR -chain locus has no D segments and is rearranged after the - chain (similar to light chain in Ig’s) o Production of a functional -chain gene -chain translation and assembly with a surrogate -chain (preT ), CD3 proteins and chain to form a pre-T cell receptor transported to the cell surface
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o Role of pre –T-cell receptor is analogous to the pre-B-cell receptor in B- cell development Triggers the thymocyte to proliferate and halt -chain gene rearrangement Ensures only one type of T-cell receptor -chain is expressed by the T cell Slides 28-30 | Unproductive Rearrangement at One -Chain Locus can lead to Rearrangement of the -Chain on the Homologous Chromosome, Rearrangement At the Same Locus Can Also Occur o This is not the case for Ig H-chain genes Exists with T-cell -chain because 2 sets of D J and C gene segments are tandemly associated with the V gene segments. Potential to “try out” up to 4 gene rearrangements = 80% of T cells make successful rearrangement of the -chain gene. Only 55% success rate for productive H-chain gene rearrangement by B cells. o Slide 29 | Rescue of Unproductive -Chain Gene Rearrangements o o Slide 30 |
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o Successful rearrangement of a -chain gene induces expression of the two co-receptors (CD4 & CD8) Called “double-positive” thymocytes Found predominantly in the inner cortex of the thymus Interact intimately with the network of epithelial cells o During cell proliferation initiated by signaling through the pre-TCR, expression of the RAG-1 and RAG-2 genes is repressed (allelic exclusion of the beta chain) o No rearrangement of the -chain genes occurs until the double-positive cells stop dividing Ensures each cell with a productive -chain gene rearrangement produces many daughter cells that have the potential to express a different -chain gene Slide 31 | T-cell Receptor -Chain Genes Can Undergo Several Successive Rearrangements o The TCR -chain can undergo several successive gene rearrangements Presence of many V and over 50 J gene segments allows many successive rearrangements (like Ig ) Almost every developing T cell will make a productive -chain rearrangement Slide 32 | Successive Gene Rearrangements Allow the Replacement of One T- cell Receptor Chain By Another Slide 33 |
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Slide 34 | Checkpoints in T-cell Development Check-point 1 - Once a beta chain is produced it is sent the ER to make sure it can bind to the surrogate alpha chain (pT ) – Pre-TCR Check-point 2 – Once an alpha chain is made it is sent to the ER to make sure it can bind to the beta chain - TCR Slide 35 | Stages of  T cell development correlate with TCR gene rearrangement and expression of cell surface proteins.
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  • Winter '17
  • GREGORYWEIGEL
  • T Cells, T Cell, development of T cells

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