T cells: Development, activation and immunity Flashcards
Knockout mice lacking MHC class II molecules
fail to produce mature CD4+thymocytes, or those clacking MHC class I molecules fail to produce mature CD8+ thymocytes, because at some level lineage commitment requires engagement between the MHC and the appropriate CD4/8 receptor.
β-Selection initiates
maturation to the DN4 stage, proliferation, allelic exclusion, maturation to the DP stage, and TCR α-chain locus rearrangement
Negative selection of tissue-specific antigens occurs
only in the medulla of the thymus, by medullary thymic epithelial cells (mTECs) and some DCs that pick-up antigens produced by mTECs.
Most thymocytes (>90%)
die of neglect in the thymus because they either did not produce viable TCR, or because they do not bind to self MHC.
Thymocyte precursors express neither
CD4 nor CD8 and enter the thymus from the bone marrow at the corticomedullary junction.
Thymocytes that bind peptide-MHC complexes with
high affinity are negatively selected.
Double-negative (DN) thymocytes progress through
several stages distinguished by expression primarily of CD44 and CD25.
Some thymocytes with autoreactive T-cell receptors
mature to become TREG cells.
Regulatory T cells help maintain
peripheral tolerance
Commitment to the CD4+ T-cell lineage is regulated by
Th-Pok
Runx3 regulates
commitment to the CD8+ lineage
Precursors of thymocytes enter the thymus at
the corticomedullary junction