BIOL 1104 Lecture Notes - Apoptosis, Stromal Cell, Peripheral Tolerance

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30 Jan 2013
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Outline of Lecture 11
T Cell Selection and Central Tolerance
I. Tolerance defined
A) Freemartin cows indicate that self tolerance is learned by developing immune
system
B) Neonatal tolerance experiment confirm Burnet hypothesis
C) Two types of tolerance
1) Central tolerance: learned during lymphocyte development (clonal
deletion)
2) Peripheral tolerance: in mature lymphocytes, multiple mechanisms (typically
results in anergy)
CENTRAL TOLERANCE
II. Step 1: TCR gene rearrangement
1) T cell starts out CD4- CD8-, migrates from bone marrow to thymus
2) TCR γ (VJ), δ (VDJ) rearrange (small subset of cells stop here)
3) TCR β VDJ rearranges, β is expressed with preTCRα (surrogate α chain, like
VpreB and λ5 in B cells); if unsuccessful, apoptosis
4) TCR α VJ rearranges (since δ locus is contained within, allelic exclusion)
5) T cell now expresses TCR αβ and CD4+ CD8+
III. Step 2: Selection
A) Selection occurs at the CD4+8+ stage to eliminate anti-self (negative
selection), but promote T cells with bad anti-self and good self-MHC (positive
selection)
B) Thymic stromal cell is involved in displaying MHC-peptide to T cell and
mediate selection
C) TCR affinity with MHC-peptide complex controls type of selection: high
affinity negative, moderate affinity positive, low affinity nonselection.
D) Positively selected cells mature into single positive T cells
IV. Step 3: Acquisition of mature effector function
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