Lec 5 coscey - -elimination of thymocytes that bind to self...

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Lec 5: T cell development II: Positive and Negative Selection 2 phases of T cell development in Thymus: -TCR production by rearrangment of TCR genes - selection o f T cells that can interact effectively with self MHC w/ moderate affinity *positive selection (TCR can interact with self MHC ) *negative selection (eliminate self-reactive cells that are strongly stim by MHC + self) Positive Selection (cortex) : -selection of T cells that are able to bind to & interact with self MHC present on thymic cortical epithelial cells -95% thymocytes die by neglect b/c don’t bind to self MHC -leads to MHC restriction ! -TCR alpha rearrangement can continue during positive selection; why? Rear =>try to bnd -expression of single positive CD4/CD8 T cells determined if TCR bind to MHCII/MHCI Negative Selection (medulla)
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Unformatted text preview: :-elimination of thymocytes that bind to self MHC with high affinity (bind too tight activation)-thymocytes here intereact w/ APC (DC + Macrophage) & medullary epithelial cells that express self Ag + MHCI/II-strong binding to self+MHC too strongly TCR signaling, activation of T cell (bad) apoptosis-some t cells reactive w/ self molec outside of thymus (problem) How to rid t cells that recognize peptides from tissue specific proteins sometimes presented by medullary thymic epithelial cells? AIRE = tf How TCR lead to either +/- selection?-TCR with diff affinities for diff peptides-avidity of TCR for particular peptide: affinity + number of peptides-avidity for diff peptides distinct signals + vs – selection...
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