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