April 10 Notes

I. T-cell receptor structure
a. Alpha and beta chains:
- actively involved in binding to antigen presented on MHC
- not involved in signal transduction
- Antigen recognition via dimer of alpha and beta chians
b. signaling chains
- involved in signal transduction in activated T-cell
- not variable
II. T-cell receptor variability
a. Constant region- part that is attached to cell membrane
b. Variable- portion that interacts with antigen presented on MHC receptors
*Hypervariable region: where TCR directly interacts with antigen
i. Complementary determining region (hypervariable region)
*CDR1, CDR2, CDR3- CDR2 mainly binds to MHC, NOT antigen (more conserved)
- CDR1 and CDR3 bind to complex of MHC and antigen
- the 3 areas can shift to create a perfect fit
ii. V (D) J recombination- process to create variability in TCR's and immunoglobulins (antibodies) from B-cells
*Each alpha and beta chain made of 2-3 gene segments
4. Promiscuous dimerization: can be α-α, β-β, or β-α
a. Whether dimmers form based on amino acid sequences of segments in respective α and β chains 5. Junctional Diversity: within hypervariable regions, hypermutable DNA sequences => especially true of regions that connect VD & J segments
a. Specific proteins act at these sites to cause random point mutations
e. T-cell receptor! Collect ‘em all!: 1013 possible T-cell receptors in one person!
*this number is more than total number of T-cells in a person
i. Sensitivity of TCRs: ~10 MHCs presenting matching antigen to TCR for TCR to bind
1. Any given mature dendritic cell has >1,000,000 MHCs presenting different antigens at a time
f. Selection for T-cell receptors: strong interaction btw TCR receptor & MHC w/antigen -> clonal expansion of
that T-cell -> T-memory cells
i. Positive selection: Thymus: selects for TCR that: strongly bind non-self antigens and weakly bind self antigens
ii. Negative selection: vast majority >99.9% of T-cells ever made are killed in thymus because they strongly bind to self antigens

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