T-CellDGRD Flashcards
What are the events in lymphocyte development?
→- Commitment
→ Proliferation
→ Selection
→Differentiation into distinct functional effector subpopulations
What are the stem cell factors important in Tcell development?
→c-KIT
Which stem cells give rise to B and T cells?
→Multipotent HSCs
What are the stages of maturation of Tcells?
→stem cell →pro-lymphocytes →pre-lymphocyte →immature lymphocyte →mature lymphocyte
What are the major events in the stem cell and pro-lymphocyte stages?
→growth factor mediated commitment
→proliferation
→initiation of antigen receptor gene rearrangement
Describe the journey of Tcells through development before proliferation
→Notch signals by the thymic stroma
→Induction of GATA3
→Commitment to the T cell lineage
→Intense proliferation
What do notch signals induce?
→commitment
Why does the thymus not increase in size?
→cells die off
Describe the T-cell journey through development
→Tcell precursor rearranges its Tcell receptor genes in the thymus
→immature T cells that recognise self MHC receive signals for survival
→those that interact strongly with self antigen are removed from the repertoire
→mature Tcells encounter foreign antigens in the peripheral lympjoid organs and are actiavted
→activated Tcells proliferation and eliminate infection
What happens 1 week after arrival of precursors into the thymus?
→progenitors commit to the T cell lineage
→Express early markers of the T cell lineage (CD2 and Thy1)
What are double negative Tcells?
→double negatives
What do thymocytes do at the DN stage?
→TCR locus
What two types of cells do DN cells divide into?
→CD3+ alpha, beta
→CD3+ gamma, delta which goes into periphery
What do Tcells express in the periphery if successful?
→TCR
Describe the structure of TCR
→heterodimer
→two transmembrane polypeptide chains
→covalently linked to each other by disulphide bonds
What are the two types of TCRs?
→alpha-beta
→gamma-delta
Describe a chain of a TCR
→Ig-like N terminal variable domain (V)
→one Ig-like constant domain (C),
→a hydrophobic transmembrane region
→a short signalling cytoplasmic region
What do the V regions of both chains contain?
→short stretches of amino acid sequence that is highly variable between receptors
What do V regions contain?
→complementary determining regions
What forms the peptide-MHC binding site?
→3 CDRs of the alpha chain
→ 3 of the beta chain
Compare the TCR and Ig system
TCR →alpha and beta components →one V domain and C domain in each chain →six CDRs → there is no change in cellular activation
Ig
→heavy and light chains
→heavy chain has one V domain, three or four C domains
→light chain has one V domain and one C domain
→six CDRs
→changes after cellular activation
What do the C regions have and do?
→cysteines residues
→bring the chains together
What residues bind to CD3 in the transmembrane region?
→charged residues
→also bind to zeta chain to form TCR