T cell Dev

Describe T cells

• Generated/Mature in?

• Subpopulations

• Generated in bone marrow,

• mature in thymus

• Sub populations:

  • T-helper cell (TH): secretes cytokines

  • Cytotoxic T lymphocyte (CTL): kills virus infected cells, tumor cells

Describe the steps in Maturation of Pro→Pre:

Maturation of Pro→Pre:

• Undifferentiated thymic progenitor stem cells from bone marrow → thymus

  • Pro-T Cell (double negative) Dev

    • Rearranging beta, gamma and delta genes

      • if Gamma/Delta assembles:

        • TCR stops further rearrangements → Commits

        • Leaves thymus → peripheral tissues

      • If Beta Assembles:

        • a pre-TCR assembles (pseudo-Alpha chain)

        • TCR stops further rearrangements → induce proliferation of CD4 and CD8

        • Continues Rearrangement of alpha, gamma and delta genes

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NOTE: after rearrangement; it is considered Pre-T

[REVIEW]

[REVIEW]

Draw out T cell dev in the thymus

Describe Positive Selection/Negative Selection

• Location

• Mechanism

Positive Selection

• Location: in cortex

• Mechanism:

  • Immature T cells or thymocytes (DP) are tested to see if they respond to a self-MHC-peptide complex

    • Low affinity/avidity recognition = keep alive

      • Thymocytes → single-positive cell + maturation continues

    • High Affinity → Death

    • No recognition = death

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Negative Selection:

• Location: In Medulla

• Mechanism:

  • mTEC (medullary thymic epithelial cells) uses AIRE (transcription factor) → express 400 different tissue-specific (self) genes → Tests the T cells

    • If affinity = too high → Death

  • NOTE: DC also contribute to antigen presentation; also helps kill high-affinity t-cells

Describe how T-reg cells are created

CD4 SP → presented w/ antigen from mTECs or BM-APCs (bone-marrow derived antigen-presenting cells) →

• if low affinity → Death

• if High affinity ubiquitous (to all tissues) → Death

• If high Affinity Tissue Restricted → Exposure to IL-2/15 → tTreg