T Cell Development-L6 Flashcards Preview

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Flashcards in T Cell Development-L6 Deck (21):
0

T cells recognize what?

Peptides derived from self or foreign antigens only when bound to self Major Histocompatibility molecules (MHC)

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CD4 T cells recognize what MHC molecule?

MHC Class II, B2 domain

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CD8 T cells recognize what MHC molecule?

MHC class I, alpha3 domain

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Where does T cell development take place?

Thymus

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Where do TCR gene rearrangements and T cell maturation take place?

Thymus

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Migration pattern of T cells

Precursors travel from the bone marrow to develop in the thymus. Mature T cells leave the thymus and travel to secondary lymphoid tissues.

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Prothymocytes

T cell precursors derived from fetal liver and bone marrow

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Site of prothymocyte entry into the thymus

Cortico-medullary junction via blood vessels

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Sphingosine-1-phosphate receptors

Control the migration process of thymocytes

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Surface markers for an uncommitted progenitor cell

CD34 (stem cell surface marker), CD44 (adhesion)

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Surface markers for a double negative (CD4/CD8) thymocyte committed to the T cell lineage

CD2 (adhesion and signaling), CD5 (adhesion and signaling), IL-7 receptor (cytokine receptor), CD1A (MHC class I like receptor)

TCR genes are beginning the rearrange

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TCR gene rearrangements

Gamma & delta chains rearrange and form receptor.

B chain gene rearranges and pre-T cell assembles. Expression of CD4 and CD8 are induced.

12

Steps to alpha chain rearrangement of TCR

Two chances for a successful B chain, if obtained then the alpha chain can attempt to rearrange many times until a functional rearrangement is produced. Then the alpha mRNA can be transcribed.

Rearrangement of alpha chain gene always eliminates the linked delta chain locus.

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Early T cell development summary

Progenitor cells proliferate to double-negative T cells, double negative T cells commit to T lineage, B genes rearrange, immature double positive cells rearrange alpha genes, then mature double positive cells

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Positive selection of alpha:Beta T cells

-Cortical epithelial cells in the thymus
-If weak or no binding to MHC the thymocyte dies
-If binding is moderate the thymocyte lives
-CD4/CD8 lineage determined by whether binding is with MHC class 1 or 2

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Negative selection of thymocytes

-If the thymocyte binds MHC too tightly it will die

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Ligands for positive and negative selection

Self peptide/MHC complexes expressed on stromal and hematopoietic cells

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AIRE transcription factor

Regulates the expression of some tissue specific antigens in medullary epithelial cells in the thymus (important in negative and positive selection--exposes thymocytes to peripheral tissue specific antigens without leaving the thymus)

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Avidity model of T cell selection

Depends on the affinity of the TCR-peptide/MHC interaction and the density of the peptide/MHC on the thymic epithelial cell. Determines the total strength of the signal delivered which dictates the outcome. Mechanism by which we get moderately binding thymocytes to MHC.

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Cell that mediates negative selection of thymocytes

Medullary epithelial cell/dendritic cell

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Regulatory T cells

Suppress autoreactive T cells by interacting with the same APC