Core Concepts-L12- CD8/MHC I

how do viral antigens get loaded into MHC I?

1. protein degradation- proteasome degrades the intracellular proteins into peptide fragments, 8-10 aa 

2. TAP- transport associated with AP moves peptide fragments from the cytosol into the ER. helps favour peptides that fit correct length and sequence for MHC I

3. in the ER- MHC I heavy chain(alpha) is sythesided and chaperones help it fold correctly. Tapasin bridges MHC I to TAP to make sure peptide fragments bind properly

4. only stable MHC-1 and peptide complexes leave the ER to the cell surface

how do peptides bind into the binding groove of MHC?

• there are anchor residues- ie must have tyrosine residues to bind here in this pocket

• physical properties of the groove- hydrophobic, pos charged or other chemical properties restrict which peptides can bind

• multiple peptides can bind as long as they have the right characteristics

how do naive CD8 T cells encounter viral antigens? why are mHC I so critical?

cross presentation helps detect viral protein

1. DCs engulf free viral particles and infected cells- loaded to MHC I.

2. naive CD8 traffic through lymph nodes and scan DCs and binds to MHC I

3. CD28 on T cell and B7 on DC ensures full activation

discuss some viral evasion mechanisms

• ICP47- blocks TAP and so peptides cant enter the ER and no MHC I loading

• E19- blocks access tapasin that stops right confirmation of MHC I

• CMV- binds MHC I and targets it for degradation and reduces MHC I on the surface

how are T cells educated? where?

educated in the thymus to ensure they respond to pathogens without attacking itself- 

1. positive- ensure T cells recognise self MHC molecules. if they cant bind to themselves die as they won’t be able to recognise other cells. if they bind too strongly also die

2. negative selection- remove T cells that bind too strongly to self peptides- APCs present self antigens expressed by AIRE