BIOL 2005 Lecture Notes - Thymocyte, T-Cell Receptor, Clonal Deletion

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30 Jan 2013
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T CELL TOLERANCE AND DEVELOPMENT
TOLERANCE – unresponsiveness to a particular ag (usually self)
self-tolerance is learned by developing immune system
FREEMARTIN condition in twin cattle: BURNET hypothesis
dizygotic twins sharing a placenta will therefore share RBC’s
developing/immature lymphocytes are subject to CLONAL
DELETION in presence if self-antigens are recognized
must occur during fetal development or early neonatal period
after that, ability to become tolerance falls off RAPIDLY
T-CELLS – more important than B-cells for tolerance
Central Tolerance – generated during lymphocyte development
involves clonal deletion
Peripheral Tolerance – generated AFTER lymphocytes have matured
involves ANERGY (inactivation)
T-CELL DEVELOPMENT: occus in thymus in 3 stages
1) TCR gene rearrangments resulting in productive α/β dimers on cell surface
α/β have many more V/J segments than γ/δ
δ is located within α this prevents α/β and γ/δ co-expression
1. V/J rearrangements in α/β and γ/δ usually α/β wins
2. β gene rearrangement completes first
3. CD4 and CD8 coexpression (but not in γ/δ)
4. if α gene rearrangement is successful α/β TCR expressed on surface
if unsuccessful cell dies
2) CELLULAR SELECTION:
Negative Selection – for self-reactive “thymocytes”
Positive Selection – recognize foreign antigens in presence of SELF MHC
3) Acquisition of mature effector function
either CD4 or CD8 is inactivated
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