T cell recognition

Question 0

TCR

Answer 0

T cell receptor
Heterodimer of alpha and beta chain
- selected through genomic recombination (VJ for alpha, VDJ for beta)
- each has 3 CDR/hypervariable regions that determine specificity bound to constant region (dimer binding, transmembrane)
Binds to MHC: peptide complex

Question 1

Dev’t of T cells

Answer 1

In thymus!!
Recombination of TCR -> alpha + beta chains
Must not react against self antigen

Question 2

TCR coreceptors

Answer 2

Increase affinity of binding -> inc signal amplification
Complementary for base of MHC complex
CD8 - MHC I alpha 3
CD4 - MHC II beta 2
CD3 is inherent part of TCR complex

Question 3

T cell costimulation

Answer 3

APCs provide second signal if they have encountered pathogens or inflammation
APC B7: T cell CD28

Question 4

T cell inactivation

Answer 4

Key for preventing autoimmunity!
Signal 1 (MHC:antigen) without Signal 2 (CD28) -> inactivation/anergy of T cell

Recognizes TCR’s that are not specific for pathogens or inflammation

Question 5

T cell: APC adhesion

Answer 5

Increases binding affinity -> signaling -> T cell response

MHC:peptide match -> APC produces chemokines -> T cell integrins activated and cluster -> adhesion

“Immunologic synapse” - integrins hold multiple TCR:MHC pairs together

Question 6

IL-2

Answer 6

Produced by T cells after activation (mostly CD4 vs CD8)
Autocrine (same cell) and paracrine (neighboring)
T cells always express low-affinity receptor -> activation -> high-affinity receptor -> stronger signal ->
clonal expansion

Question 7

CTLA-4

Answer 7

Expressed on T cells after activation
Out-competes CD28 for B7 binding (on APC)

Inhibits T cell (ends immune reaction)

Question 8

Superantigens

Answer 8

Produced by bacteria
Non-specifically link MHCs to TCRs via beta chain
-> non-antigen specific activation of multiple/polyclonal T cells

Overwhelming activation (>80%) vs normal infection ( cytokines, immune cascade -> BAD
Ex: toxic shock syndrome