L10 - Properties of the TCR

Question 1

What is the difference between TCR recognition and BCR?

Answer 1

TCR can only recognize small peptide in the context of MHC

- Low affinity interaction

Question 2

Describe briefly the TCR

Answer 2

Monovalent compared to BCR, composed of an alpha chain (Vα, Cα), (Vβ, Cβ) and a transmembrane domain

Question 3

What are the CD3 molecules near TCR?

Answer 3

Four distinct chains. Contains a CD3γ, a CD3𝛿 and two CD3ε chains.

Although not part of it, it associates with the ζ chain as well as the TCR to form the TCR complex

Question 4

What does ITAM stand for?

Answer 4

Immunoreceptor Tyrosine-based Activation Motif

Question 5

Where are ITAMs found?

Answer 5

Conserved sequence of four amino acids found on the cytoplasmic tails of CD3 chains and ζ chain

Question 6

T/F: All TCRs are αβ

Answer 6

F. γ𝛿 TCRs exist, not CD4-CD8- and not classically MHC restricted. Unknown function

Question 7

With respect to the gene segments, what chains between the lg and TCR are similar?

Answer 7

• Heavy chain of Ig and β chain of TCR (Both VDJC)

- Light chain of Ig and α chain of TCR (Both VJC)

Question 8

TCR genetics is quite similar to BCR with what difference?

Answer 8

TCR genes do not undergo somatic hypermutation

Question 9

How does the α gene compare to the light chain of the BCR?

Answer 9

Similar to the κ chain, Vα–Vαn–Jα1-50–Cα. Separated segments

Question 10

How does the β gene compare to the heavy chain of the BCR?

Answer 10

In heavy chain of BCR, V D J and C segments are all compartmentalized. In the β gene, D and J and C occur in tandem
Vβ1–Vβn–Dβ1-Jβ1.1-1.6-Cβ1–Dβ2-Jβ2.1-2.6-Cβ2

Question 11

What CDR region makes dominant contact with the peptide?

Answer 11

CDR3

Question 12

What are superantigens?

Answer 12

Antigens made by some microorganisms e.g. TSST (Toxic shock syndrome toxin)

• Binds directly to TCR and MHC Class II without processing, the 4th hypervariable loop of TCR β-chain
• Selects TCR based on only Vβ sequence
• Can activate up to 10-20% of all TCRs

Question 13

What are the effects of MHC on transplantation

Answer 13

• T cells recognize self MHC + foreign peptide
• Allogenic responses are often strong
• The more HLA mismatches, the lower rate of long term graft survival

Question 14

Briefly describe positive and negative selection

Answer 14

• Need to bind to self MHC (positive) but those bound too strongly are deleted (negative)

Question 15

Describe different forms of allorecognition

Answer 15

• Self MHC-restricted T cell recognizes an allogenic MHC molecule whose structure resembles a self MHC-foreign peptide complex
• Self MHC-restricted T cell recognizes a structure formed by both allogenic MHC molecule and bound peptide (not the same)
• Molecular mimicry e.g. viruses