Antigen presentation by MHC class I

Question 1

Which part of the virus is recognised by cytotoxic t lymphocytes (CTL) ?

Answer 1

When the virus infects a cell, the cell displays viral antigens - this can include soluble secreted proteins, proteins inserted into the membrane, and proteins inside the cell

Question 2

What type of viral antigen presentation is linked to MHC class I?

Answer 2

transplantation antigen

Question 3

Antigen Processing and Presentation Pathway

Answer 3

How the large proteins expressed inside the cell are processed (broken down to small peptides) and bound to MHC class I

Question 4

BROADLY - the 6 steps of the antigen processing and presentation pathway in MHC class I

Answer 4

1) Viral antigens in the cytosol of the infected cell are degraded by the proteasome complex
2) Peptides moved from cytosol to ER by TAP. Active process
3) Peptide binds to MHC class I
4) Protein loading complex -> accessory molecules to binding
5) Assembly of MHC class I/peptide complexes
6) Peptides further trimmed in ER

Question 5

Proteasome action

Answer 5

Proteins targeted for degradation are modified by addition of ubiquitin
Proteins are unfolded and fed through the centre of the core particle
Generates about 5-15 amino acids

Question 6

TAP

Answer 6

Heterodimeric complex of TAP1 and TAP2
ATP-binding cassette (ABC) family of transporters
Transports peptides of 8-13 amino acids from the cytosol to the ER

Question 7

Peptide binding to MHC class I

Answer 7

Peptide binding groove exists between alpha one and alpha two helices
Peptide is bound with both ends tightly at either side of the cleft
Peptides are mostly 8-9aa long
Peptide motifs have been found for each HLA allele studied

Question 8

Assembly of MHC class I/peptide complexes

Answer 8

MHC class I heavy chain first associates with calnexin
Class I heavy chain folds to form binding-capable beta 2 microglobulin
Calnexin is replaced by calreticulin
Tapasin & ERp57 associate with the complex -> generate PLC