T Cell Development Flashcards
where does early T cell precursor development occur?
bone marrow
what happens when cells arrive at the thymus?
their T cell receptors are committed to the T lineage by a receptor called Notch
when the T cell precursors arrive at the thymus, what is the stage called and what does it mean?
- double negative stage
- they lack CD4 and CD8 as well as their T cell receptor is not fully assembled
what does each TCR peptide contain?
- variable region containing CDRs
- constant region containing transmembrane regions
what are the four types of peptides that are used for T cell receptor assembly?
alpha, beta, gamma and delta
which T cells are CD4 or CD8 positive and found in the lymph nodes or spleen?
T-alpha-beta
what do T-alpha-beta cells recognize and do?
- protein antigens
- bind to antigen derived peptides and MHC
what T cells are CD4 or CD8 negative and predominate on the skin and mucosal surfaces?
T-gamma-delta
what do T-gamma-delta cells recognize?
- lipid antigens
- do not use MHC for antigen recognition
what are the four mechanisms to produce a diverse repertoire of antigen-MHC binding sites for T cells?
- selection of mini genes
- recombination
- addition and deletion
- association of two different chains to form binding sites
do somatic hypermutations occur during T cell binding site production?
no
what happens if B-chain rearrangement is productive?
it pairs with a surrogate α-chain (called pre-Tα) to form a pre-TCR complex which sends signals that stop further β-chain rearrangement and promote the rearrangement of the α-chain, ultimately forming a complete TCRαβ receptor.
what happens if B-chain rearrangement is non-productive
the cell can instead rearrange the γ and δ chains, forming a TCRγδ receptor
what happens when Tαβ cells become double positive?
- they express both the CD4+ and CD8+ that travel through the cortex and are selected based on their affinity for MHC class I and II molecules
what happens if the Tαβ cells recognizes and binds to MHC Class I molecules?
the cell is instructed to become CD8+ single-positive (SP) (cytotoxic T cell) in the medulla
what happens if the Tαβ cells recognizes and binds to MHC Class II molecules?
the cell becomes CD4+ single-positive (SP) (helper T cell) in the medulla
what are major histocompatibility complex (MHC) molecules?
- self identity molecules that have broad binding specificity that carry many different peptides including self peptides that bind to TCR and CD4/8 domains
where is MHC I and II found?
MHC I: almost every cell (nucleated)
MHC II: antigen presenting cells
CD8 molecules on T cells bind to what domain of MHC I?
alpha-3
CD4 molecules on T cells bind to what domain of MHC II?
beta-2
when is a T cell positively selected?
if its TCR binds the MHC-peptide with moderate affinity
what happens if T cells cannot bind to MHC peptide during positive selection?
they die of neglect
what happens during negative selection of T cells?
-medullary thymic epithelial cells (mTEC) containing autoimmune regulator protein (AIRE) express and present self antigens all over the body
- T cells that bind too strongly to those self-antigens are eliminated to prevent autoimmunity or develop into regulatory T cells.
how are regulatory T cells developed and what do they do?
- some thymocytes that see self-antigens in the thymus differentiate to CD4+, regulatory T cells.
- leave the thymus and inhibit responses against self-tissues in the periphery.
