Antigen Presentation Flashcards
B cells recognize what kind of antigen ?
Antigen in its native form
T cells recognize what kind of antigen ?
Processed antigen presented by MHC on another cell
Differentiate T cells based on MHC class
T cytotoxic: binds MHC I
T helper: binds MHC II
__ are polygenic, polymorphic, and co-dominant. What does this mean ?
MHC are:
- polygenic - multiple genes
- polymorphic - multiple alleles for each gene
- co-dominant - paternal and maternal genes are co-expressed
MHC I structure
3 alpha domains + Beta microglobulin
MHC I binds to… (2)
TCR of T cytotoxic cells + CD8
MHC I: antigen/ peptide size and fit
8 - 11 amino acids in a CLOSED GROOVE
MHC I: Where do antigens/ peptides come from and go in the cell ?
- Come from inside cell (ENDOGENOUS)
- loaded into Endoplasmic Reticulum
MHC I are on which cells ?
All NUCLEATED cells
MHC II structure
Two peptide chains:
2 alpha + 2 Beta domains
MHC II binds to… (2)
TCR of T helper cells + CD4
MHC II: antigen/ peptide size and fit
12 - 22 amino acids in an OPEN groove
MHC II: Where do antigens/ peptides come from and go in the cell ?
- come from outside the cell (EXOGENOUS)
- processed into the ENDOSOMAL/ENDOCYTIC pathway
MHC II are on which cells ?
Professional APCs and cytokine-activated cells
Describe how endogenous antigens are generally processed (3)
- In cytoplasm, ubiquitin + ATP = proteasome digests antigens into peptides
- TAP channels peptides into Endoplasmic Reticulum
- Peptides are loaded onto MHC I
Describe how exogenous antigens are generally processed (3)
- Exogenous antigens are endocytosed/ phagocytosed
- Endosomal proteases digest antigens into peptides
- Peptides loaded onto MHC II
List 2 type of antigens that follow the endogenous pathway
- Peptides from replicating viruses (that have entered cells)
- Intracellular misfolded self-peptides
Describe: TAP
Transporter associated with Antigen Processing:
- ATP-dependent
- ONLY transports 8-16 amino acids (for MHC I) from Cytoplasm to Endoplasmic Reticulum
Immunoproteasome vs proteasome
Proteasome:
- proteases (β1, β2 and β5) degrade faulty proteins
Immunoproteasome:
- proteases (β1i, β2i and β5i) activated by IFNy or TNFa during an infection
- professional APCs contain Immunoproteasomes
Described assembly of MHC I with peptides
- completed in the RER
- calnexin and ERp57 direct partial folding of α chain
- β2 microglobulin binding = calnexin released
- calreticulin and tapasin brings complex near TAP (which transports peptides into RER from cytoplasm)
- ERAP reduces size of peptides to fit MHC I binding groove (8-11 a.a)
- stabilized MHC I = release of tapasin, ERp57, and calreticulin
NOTE: only calnexin, ERp57, and calreticulin are molecular chaperones
Summary of MHC I Endogenous pathway (4)
- Endogenous antigen is degraded by Immunoproteasome
- TAP transports peptides from cytoplasm to RER
- calnexin, ERp57, calreticulin, tapasin, and ERAP = assembly of MHC I and peptide (8 - 11 a.a) in RER
- MHC I and peptide transported from RER > golgi > plasma membrane
Cells that express MHC II, bind MHC II, and type of peptides on MHC II
- only professional APCs express MHC II + deliver co-stimulatory signal
- only peptides from exogenous bacteria/ viruses/ self-proteins are processed
- CD4+ T helper cells recognize MHC II antigens
Differentiate professional vs non-professional APCs
ACPs:
- expresses MHC II (and MHC I)
- able to deliver a co-stimulatory signal
Professional:
- dendritic
- macrophage (must be activated by phagocytosis)
- B cells (must be activated by antigen)
Non-professional:
- endothelial cells (must be activated by cytokines ie. IFNy)
Describe generation of peptides in endocytic vesicles via MHC II exogenous pathway
- antigen on BCR is enclosed by clathrin-coated vesicle
- progression from early (pH 6.0 - 6.5) to late endosome (pH 4.5 - 5.0)
- MHC II from golgi combines with late endosome
- proteases in late endosome hydrolyzes antigens into peptides (12-22 a.a)
Describe transport of MHC II into endocytic vesicles
- α and β chains made in RER
-
invariant chain immediately binds:
– chaperone facilitates folding
– prevents peptides in RER from binding MHC II
– directs MHC II from RER to endosome
NOTE: three MHC II + three invariant chains = stable nonamer
Describe assembly of MHC II with peptides
- from early to late endosome, pH decreases
- invariant chain is gradually degraded EXCEPT CLIP remains in the binding groove
- HLA-DM replaces CLIP with peptide (12-22 a.a) = stable MHC II and antigen
- HLA-DO can bind to HLA-DM = negatively regulates activity
What happens when MHC I cannot be expressed on cell surface ?
Bare Lymphocyte Syndrome Type 1:
- decreased surface MHC I
- mutated TAP
- decreased T cytotoxic cells
= viral, respiratory bacterial infections
= necrotizing skin lesions
= excessive NK activation
What happens when MHC II cannot be expressed on cell surface ?
Bare Lymphocyte Syndrome Type 2:
- decreased surface MHC II
- transcription factor defects
- decreased T helper cells
= severe combined immunodeficiency syndrome
= cannot help B cell or T cytotoxic response
What is CD1 ?
- heavy chain + β2 microglobulin (resembles MHC I)
- presents self-lipids and LPS + mycolic acids from bacteria
Four mechanisms for uptake of foreign lipid:
- apoliprotein complexes bound to LDLR
- Phagocytosis by pathogens
- C-type lectins bind mannose residues on glycolipids
- Scavenger receptors bind modified LDL and apoptotic cells
NOTE: CD1e and saposins all extract from membrane and transfers to CD1
