T Cell Development-L6 Flashcards
CD4 T cells recognize what MHC molecule?
MHC Class II, B2 domain
T cells recognize what?
Peptides derived from self or foreign antigens only when bound to self Major Histocompatibility molecules (MHC)
CD8 T cells recognize what MHC molecule?
MHC class I, alpha3 domain
Where does T cell development take place?
Thymus
Where do TCR gene rearrangements and T cell maturation take place?
Thymus
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.
Prothymocytes
T cell precursors derived from fetal liver and bone marrow
Site of prothymocyte entry into the thymus
Cortico-medullary junction via blood vessels
Sphingosine-1-phosphate receptors
Control the migration process of thymocytes
Surface markers for an uncommitted progenitor cell
CD34 (stem cell surface marker), CD44 (adhesion)
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
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.
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.
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
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
Negative selection of thymocytes
-If the thymocyte binds MHC too tightly it will die
Ligands for positive and negative selection
Self peptide/MHC complexes expressed on stromal and hematopoietic cells
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)
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.
Cell that mediates negative selection of thymocytes
Medullary epithelial cell/dendritic cell
Regulatory T cells
Suppress autoreactive T cells by interacting with the same APC
