What are the two major compartments of the cell?
Cytosol and nucleus and vesicular system (ER, Golgi, vesicles, lysosomes)
Why are these two compartments kept separate?
Separate intracellular vs extracellular problems and prevent incorrect protein interactions
How is material moved between them?
Transport proteins (energy required)
Relationship between MHC I and endogenous antigens?
MHC I presents intracellular proteins (viral, tumor, self)
How does antigen presentation work under healthy conditions?
Self-antigens are presented
How does antigen presentation work during infection?
Foreign antigens are presented → immune response
Self vs non-self antigen?
Self = body proteins; Non-self = pathogens
Is self-antigen presentation bad?
❌ No → normal monitoring process, monitors cell health and maintain tolerance
What is ERAD?
Misfolded ER proteins → sent to cytosol → degraded by proteasome
What is the proteasome?
Degrades proteins into peptides
What is the immunoproteasome?
Modified version → better peptides for MHC I
What causes the switch?
IFN-γ (inflammation)
What is a Constitutive proteasome?
Normal version in healthy cells
In what cellular compartments do various stages of MHC class I presentation take place?
Cytosol → protein breakdown, ER → peptide loading, and Surface → presentation
Role of TAP (Transporter Associated w/ Antigen processing)?
Moves peptides from cytosol → ER
Role of calnexin?
Helps MHC I fold properly and stabilizes the alpha chain before peptide loading
What are the components of the peptide loading complex?
Tapasin, peptide editing, ERp57, Calreticulin and (MHC Class 1 and β2M)
Function of Tapasin?
Links MHC I to TAP + peptide editing
What is peptide editing?
helps select high-quality peptides improving the stability of MHC 1 complex.
Function of ERp57?
Protein folding helper (Chaperone)
Function of Calreticulin?
Stabilizes MHC I during loading
Function of MHC I + β2M?
Form presentation complex
What is ERAP?
an ER aminopeptidase and it trims peptides to correct size for MHC 1
What is immunodominance?
Few peptides dominate T cell response
What is the purpose of presentation of self-antigen?
Allows external antigens → MHC I→ activates CD8 T cells
Is this presentation bad or normal?
This is a normal process
Purpose of Cross-presentation?
It allows for exogenous antigens to be presented on MHC 1 which is important in activating CD8 T cells against viruses and tumors.
Three major APCs?
Dendritic cells, macrophages, B cells
Which APCs initiates adaptive immunity?
Dendritic cells
What do dendritic cells do in antigen presentation?
Capture antigen → go to lymph node → activate T cells
Relationship between MHC class 2 and exogenous antigen?
MHC Class 2 presents exogenous (external) antigens
How do exogenous antigens enter cells?
Endocytosis or phagocytosis
Purpose of invariant chain?
1. Blocks binding groove 2. Sends MHC II to endosome
What is CLIP?
fragment of invariant chain that temporarily occupies a binding groove
What is HLA-DM?
Intracellular APCs that removes CLIP + loads real antigen
What presents lipid antigens?
CD1 family molecules
How are CD1 family molecules similar to MHC I?
its structure, using a binding groove to present antigen and expressed on the cell surface
How are CD1 family molecules similar to MHC II?
presenting exogenous antigens and antigens being processed in vesicular/ endosomal compartments.
What cell type do CD1 family present to?
NKT cells
CD8 T cell function?
Kill infected/cancer cells
CD4 T cell function?
Help immune response (activate macrophages, B cells, regulate)
Difference between MHC I vs MHC II?
MHC I → intracellular → CD8 and MHC II → extracellular → CD4