2-17 T-Cell Receptor and MHC

Question 1

What is the general role of T cells?

Answer 1

Question 2

How do T-cell and B-cell receptors differ?

Answer 2

Variability: NO SOMATIC HYPERMUTATION in TCRs

Expression: BCRs can be expressed at the cell surface OR secreted; α:β TCRs are expressed at the cell surface only

Antigen recognition: BCRs recognize proteins, carbohydrates, and lipids; α:β TCRs recognize short peptides only

Antigen binding: BCRs have 2 binding sites; α:β TCRs have only 1

Affinity: BCR >> TCR

Function: BCRs both recognize and effect; TCRs recognize only

Question 3

What is the structure of the T-cell receptor (TCR) complex?

Answer 3

• 8 polypeptides
• α and β chains bind antigen and form the core T-cell receptor (TCR)
• Each α and β chain associates with 1 copy of CD3γ, 1 copy of CD3δ, 2 copies of CD3ε, and 2 ζ chains
• These assoc., invariant polypeptides are necessary for the transport of newly synthesized TCR to the cell surface and for the transduction of signals to the cell’s interior after antigen binding

(Below, αβ TCR)

Question 4

How do the two TCR classes differ?

Answer 4

α:β and γ:δ TCRs have similar structures (α≈γ, β≈δ) but are encoded by different gene rearrangements and have different functions.

1. α:β T cells: majority population in blood; functions in adaptive immunity; recognizes MHC-bound antigen only
2. γ:δ T cells: majority population in tissue; fewer V gene segments than α:β, but more junctional diversity; function unknown, but involved in surveillance, gut immunity; NOT restricted to recognition of MHC-bound peptide antigens

Question 5

How do the two MHC classes differ?

Answer 5

Question 6

How do MHC class I molecules present antigen?

Answer 6

• Proteasome ubiquinates, fragments newly synthesized proteins →
• Peptides attach to TAP protein in ER membrane →
• Peptide-TAP complex moves into ER lumen of the ER →
• Peptide placed in binding groove of MHC Class I, displacing self peptide
• Class I:peptide goes to the cell surface

Question 7

How do MHC class II molecules present antigen?

Answer 7

• Ingested antigens taken into phagolysosome and fragmented by proteases →
• Peptides move to endosomal compartments →
• Peptides placed in binding groove of MHC Class II, displacing class II-associated invariant-chain peptide (CLIP) →
• Class II:peptide carried to the cell surface

Question 8

What is an MHC haplotype?

Answer 8

The complete set of alleles found within an animal’s MHC. One MHC allele is inherited from each parent, and both alleles are expressed on cells co-dominantly.

Most divergent haplotypes will present more peptides from any pathogen than more related haplotypes, so they are able to activate more pathogen-specific T cells.

Question 9

What causes MHC polymorphism, and why is it important?

Answer 9

Allelic variation causes polymorphism at the classical MHC loci, which affects the binding and presentation of peptide antigens to T cells.

Rejection of transplanted organs and some diseases may be associated with specific MHC types. Disease relative risk can be determined by:
(MHC+/MHC-) ppl w/ disease ÷ (MHC+/MHC-) w/o

Question 10

How does MHC restrict presentation of antigen to α:β T cells?

Answer 10

Any given TCR is specific for the complex of a particular peptide bound to a particular MHC molecule.

Though the anchor residues that bind a peptide to an MHC molecule are buried, the peptide’s various other positions form part of the planar surface that interacts with the TCR.

A T cell that responds to a peptide presented by one MHC allotype will not respond to another peptide bound by that same MHC allotype or to the same peptide bound to another MHC allotype.

Question 11

What is a superantigen?

Answer 11

An antigen that can act as bridge between TCR and MHC and stimulate a high percentage of T cells bearing certain V genes.

ex) Toxic shock syndrome