MHC Flashcards
Major histocompatibility complex (MHC)
Presents portions of antigens to specific T cells
Antigens are noncovalently bound to MHC calls 1 and 2 molecules and each T cell is specific only to its class of MHC
MHC 1 : CD8
MHC 2 : CD4
What do NK cells do?
Go throughout the blood system and kills any cell that is not expressing self-MHC class 1 molecules
- counters common viral strategy to down regulate MHC 1 on infected cells
B cell epitopes
Specific surface piece of antigen or secreted molecule/toxin to which antibody binds to
- is conformational and linear
T-cell epitopes
Specific piece of antigen that is held by and MHC molecule and presented on the surface of an APC
- must be linear
Class 1 vs Class 2 MHC
MHC 1: expressed on almost all uncleared cells and binds with CD8 T-cells (cytotoxic)
MHC 2: expressed on professional APCs only (ex: dendritic cells) and binds with CD4 T-cells (helper)
Capture of antigens steps
Pathogens enter through various epithelium and bind to APCs where they are killed and processed into antigens
APCs then migrate into draining lymph nodes via afferent vessels and either bind to dendritic cells of directly to T cells
Antigen specific T cells proliferate and take on effector functions once activated by MHC interaction.
T-cells then migrate out into blood system via efferent vessels to find the infection
Professional APCs are resident in all tissues and protect by taking up and processing antigens
What is the “grand central station” of the immune system?
Lymph nodes
Expect for blood borne pathogens, in this case it is the spleen
How do DCs known to go to the nearest lymph node?
Via chemotaxis through inflammatory signals from the infected lymph node (use IL-1, IL-6 and TNF a cytokines)
- the inflammation cytokines trigger DCs to lose adhesiveness for epithelial and express CCR7
- CCR7 is the receptor that binds to cytokines released by lymph nodes at all times and tells the DC where to go
Cells in lymph nodes
Dendritic cells: high amount of MHC class 2 and co-stimulators activity
Macrophages: high amount of MHC class 2 but must be stimulated by something else (usually TNF-y)
Bcells: high amounts of MHC class 2 but must be stimulated by cytokines to gain co-stimulators molecules
B cells more concentrated in cortex, T cells more concentrated in medulla
Difference between class 1 and 2 MHC structurally
Class 1: contain 2 alpha chains with a noncovalently associated beta chain via B2m molecules
Class 2: contains 1 alpha and 1 beta chains with covalent bonds
MHC binding clefts
Not very specific with 2,000 possible different Allele combos
- each peptide presents with 100-4000 copies in cells
MHC class 1 peptide interactions
Are 8-10 AAs - AAs essential for binding peptides to MHC class 1 molecules = anchor residues
- binding cleft is closed
All nucleated cells express MHC class 1
MHC class 2 peptide interactions
Are 10-30 AAs
-cleft is open at both ends (kinda like a hotdog)
Use conserved motifs to bind things in the cleft (not anchor residues)
MHC class 1 peptide loading
Cytosolic pathway/endogenous
1) pathogen protein gets ubiquitinated once it enters cells
2) proteasomes in cells chop up ubiquinated proteins into peptides
3) Transporter Associated w/ antigen Processing (TAP) uses ATP to translocations peptides into the ER lumen
4) tapasin links empty class 1 to TAP via chaperone proteins to prepare binding of incoming peptide
5) peptide fitting into binding cleft releases chaperone proteins and the stable MHC w/ peptide is transported to the surface via golgi
MHC class 2 peptide loading
Exogenous/endocytic pathway (extracellular antigens)
1) MHC class 2 molecules are synthesized and assembled in ER, alpha and beta chains are brought together via chaperone proteins to the invariant chain
2) MHC with invariant chain is transported to the MHC class 2 compartment
3) antigenic protein gets taken up by APCs into endoscopes
4) proteins become target of proteasomes within the endoscopes as pH drops and chops the antigenic proteins into peptides in the endoscopes, which then fuse with the MHC class 1 compartment.
5) enzymes digest the invariant chain at the same time leaving only Class 2 invariant chain peptide (CLIP) left which then binds to the peptides in the endosome and gets replaced with antigen peptide via HLA-DM when an antigen peptide is present
6) stable MHC 2 w/ peptide is transported to the surface
