MHC Molecules Flashcards
Function of MHC molecules
T cells only recognize peptide epitopes when complexed with an MHC molecule
APCs “present” these peptide/MHC complexes to the T cells via their TCR
Haplotype
Each individual has six class I genes (3 maternal, 3 paternal), and six class II genes (3 maternal, 3 paternal) which is referred to as their haplotype
Why is it important that MHC molecules be “matched” between an organ donor and a recipient?
If MHC molecules don’t match, they will not be recognized by the receiver’s T cells and IR will occur!
- MHC are the molecules mostly responsible for graft/transplant rejection (minor HC, or MHC, are also partly the cause- even when MHCs are matched)
______ makes it very unlikely that two unrelated individuals will express identical sets of MHC proteins and is the reason donors and recipients must be a “match”
Extensive polymorphism
MHC Restriction
T cell can interact with both the MHC and the foreign peptide that is bound to it, but will recognize and respond to the antigen, only when it is bound to a particular MHC molecule that it recognizes as self
- reason why thymocytes need to be educated in the thymus to recognize one’s own MHC molecules
Class Restriction
T cells are class restricted
- CD4 T cells recognize MHC Class II
- CD8 T cells recognize MHC Class I
When an APC presents Ag on MHC class I, it is recognized by a _____________. This causes ___________
CD8 T cell
This causes the CD8 T cell to differentiate into CTL clones initiating the cell-mediated response
When a CTL recognizes a foreign peptide presented by MHC class I on a non-APC cell in the body, the CTL then ______
Kills that cell known as cell-mediated immunity (CMI)
Cells routinely “present” self-peptides on MHC Class I molecules to __________
Show the immune system the cell is healthy
When an APC presents Ag on an MHC Class II, it is recognized by a _______. This causes ______________
CD4 T cell
This causes the CD4 T cells to differentiate into clones of one of the different types of T helper cells.
Depending on which type of Th cells results from CD4 T cell activation, it could lead to humoral or cell-mediated immunity.
Purpose of MHC restriction
To tell between self and non-self
SELF MHC molecules- no immune response
FOREIGN MHC - immune response
What would happen to a cell that failed to display self-peptides in MHC Class I molecules?
Autoimmunity
Nomenclature: MHC Class I proteins
HLA-A#, HLA-B#, HLA-C#
Nomenclature: MHC Class II proteins
HLA-DP#, HLA-DQ#, HLA-DR#
MHC Class I structure
Composed of a single alpha chain with 3 domains- alpha 1,2,3
Each alpha chain pairs with non-MHC gene product- Beta-2 microglobulin
MHC alpha chain is polymorphous (occurring in many different forms), but the Beta2-m is invariant
MHC Class I - peptide binding
Anchor residues tend to be on the ends of class I peptides - may be acidic or basic anchor residues
Peptide loading occurs in the ER
A variety of peptides are “tried on” by the various class I molecules - if a peptide does not fit any of the class I molecules, it is returned to the cytoplasm for further processing
Once a peptide is loaded, the peptide-MHC complex moves to the surface where it is displayed for CD8 T cells, CTLs, and NK cells
Peptides displayed on class I molecules are derived from ________
Endogenous antigens ie proteins made inside the cell
May be from intracellular pathogens inside the cytoplasm or nucleus or self (host cell) peptides
Processing of endogenous antigens occurs in the ________ by the ________
Cytoplasm; proteasome
MHC Class I endogenous pathway- Processing
- Protein shuttled to the proteasome for degradation
- Pathogens phagocytosed and transported to cytosol
- MHC Class I will bind host and foreign peptides
- CTL will either recognize MHC-peptide complex —> kill or not!
- When host cell is infected with intracellular pathogen, it produces cytokine IFN-gamma
- IFN-gamma causes upregulation of MHC locus for expression of more MHC molecules (note: this process can be interrupted by some pathogens in order to inhibit the Ag presentation process)
- IFN-gamma also induces changes in the structure of the proteasome to more readily process endogenous proteins = Immunoproteasome
MHC Class I endogenous pathway- peptide trafficking summary (3)
1) Peptide loading of Class I in the ER
- peptides tried on on by class I MHC
2) MHC:Peptide complex transported through the golgi to the cell surface
3) These complexes will be checked by CTL’s for recognition- if recognized, the cell will be killed by the CTL
MHC Class I endogenous pathway- peptide trafficking. Explain in detail with transporters etc (4)
Some peptides are bound by special transport proteins called TAP-1 and TAP-2 (transporter associated with antigen processing) which move the peptides into the ER (using ATP) to be loaded onto the class I molecules
Class I molecules in the ER are stabilized by calnexin (chaperone protein).
- also prevents premature exit of unloaded Class I molecule from the ER
The class I molecule then associates with tapasin which brings TAP and the class I molecule closer together for loading
Once loaded, the peptide:MHC complex is transported through the Golgi to the cell surface
MHC Class 1 are expressed on
Nearly all nucleated cells
MHC Class II are expressed on
APCs- DCs, B cells, and macrophages ;
MHC Class II structure
Each class II molecule consists of two proteins, each with two domains
- Alpha chain: alpha1 & alpha2 domains
- Beta chain: beta1 & beta2 domains
Peptide binding cleft is comprised of the alpha1 and beta1 domains which accommodates peptides of a variety of lengths- 13 to 25 amino acids
Anchor residues are spaced along the length of the peptide, not just at the ends
Since the MHC class II molecule is made up of 2 proteins, they can consist of __________________
1 chain from each parent making even more combinations
MHC Class II - peptide binding
Peptide loading occurs inside the vesicles where the phagocytosed pathogens are located.
Anchor residues spaced along the length of the peptide,not just at the ends
Class II peptides are derived from _______________
Exogenous antigens
- proteins made outside the cell & brought in already formed
- Or Intravesicular pathogens: peptides made in the phagosome (ie technically “inside the cell but not in the cytoplasm”)
MHC Class II Exogenous Pathway- Processing
Processing of the antigenic proteins occurs in the phagolysosome acidic vesicle
- pathogen is phagocytosed
- lysosome fuses with phagosome (phagolysosome)
- pH is reduced (H+ ions pumped in)
- enzymes, such as cathepsins, kill pathogen & break down proteins into peptides to be loaded onto the class II molecules
MHC Class II Exogenous pathway- Trafficking (6)
- MHC class II molecules are synthesized and assembled in the ER (same as Class I). Invariant chain occupies the binding cleft
- Class II invariant chain complex buds off from the Golgi complex in a membrane-bound vesicle
- Invariant chain is cleaved, leaving only a small portion in the binding cleft called the CLIP (Class II associated invariant peptide)
- the vesicle with the Class II:CLIP complex fuses with the phagolysosome
- HLA-DM removes the CLIP and facilitates peptide loading
- after loading, the MHC class II:peptide complex moves to the surface of the APC
Intravesicular pathogen-
Different from intracytosolic?
Peptides being made in the phagosome technically “inside the cell but not in the cytoplasm”
Intracytosolic pathogen- makes proteins in the cytosol that are accessible to the proteosome
What type of antigens are presented by CD1 molecule?
Lipid, glycolipid, and phospholipid antigens can be presented to a small subset of non-classical (non-CD4 and non-CD8) T cells via CD1
Example of a bacteria that is presented via the nonclassical pathway?
Involved in stimulating an adaptive immune response to Mycobacteria species which are rich in lipids
Clinical correlate: A defect in the class I (endogenous) pathway leads to increased ____________
Viral (intracellular) infections
A defect in the class II (exogenous) pathway leads to increased _________
Bacterial (extracellular) infections
Is β2 macroglobulin polymorphic?
No it is invariant ie never changes
MHC molecules are polymorphic
What is meant by promiscuous binding?
Each MHC molecule is capable of dining many different antigenic peptides (reason for this: 1000s of antigenic peptides)
What is the function of the invariant chain in the presentation of exogenous antigens?
- Chaperone for proper folding of Class II MHC molecules
- Prevent binding by endogenous peptides while in ER
- Traffics Class II MHC to endosomal pathway where peptides can be loaded in vesicle where pathogen was killed (phagolysosome)
What is the function of HLA-DM in the presentation of exogenous antigens?
Removes the CLIP and facilitates peptide loading
What are the roles/functions of TAP, tapasin, and calnexin in the presentation of endogenous antigens?
- TAP moves peptides to the ER (using ATP)
- Calnexin stabilizes MHC class I in the ER. Also prevents premature exit of an unloaded class I molecule in the ER
- Tapasin moves TAP and Calnexin closer together to facilitate peptide loading
Is β2 macroglobulin polymorphic?
No it is invariant ie never changes
MHC molecules are polymorphic
What is meant by promiscuous binding?
Each MHC molecule is capable of dining many different antigenic peptides (reason for this: 1000s of antigenic peptides)
What is the function of the invariant chain in the presentation of exogenous antigens?
- Chaperone for proper folding of Class II MHC molecules
- Prevent binding by endogenous peptides while in ER
- Traffics Class II MHC to endosomal pathway where peptides can be loaded in vesicle where pathogen was killed (phagolysosome)
What is the function of HLA-DM in the presentation of exogenous antigens?
Removes the CLIP and facilitates peptide loading
What are the roles/functions of TAP, tapasin, and calnexin in the presentation of endogenous antigens?
- TAP moves peptides to the ER (using ATP)
- Calnexin stabilizes MHC class I in the ER. Also prevents premature exit of an unloaded class I molecule in the ER
- Tapasin moves TAP and Calnexin closer together to facilitate peptide loading
Is β2 macroglobulin polymorphic?
No it is invariant ie never changes
MHC molecules are polymorphic
What is meant by promiscuous binding?
Each MHC molecule is capable of dining many different antigenic peptides (reason for this: 1000s of antigenic peptides)
What is the function of the invariant chain in the presentation of exogenous antigens?
- Chaperone for proper folding of Class II MHC molecules
- Prevent binding by endogenous peptides while in ER
- Traffics Class II MHC to endosomal pathway where peptides can be loaded in vesicle where pathogen was killed (phagolysosome)
What is the function of HLA-DM in the presentation of exogenous antigens?
Removes the CLIP and facilitates peptide loading
What are the roles/functions of TAP, tapasin, and calnexin in the presentation of endogenous antigens?
- TAP moves peptides to the ER (using ATP)
- Calnexin stabilizes MHC class I in the ER. Also prevents premature exit of an unloaded class I molecule in the ER
- Tapasin moves TAP and Calnexin closer together to facilitate peptide loading
Is β2 macroglobulin polymorphic?
No it is invariant ie never changes
MHC molecules are polymorphic
What is meant by promiscuous binding?
Each MHC molecule is capable of dining many different antigenic peptides (reason for this: 1000s of antigenic peptides)
What is the function of the invariant chain in the presentation of exogenous antigens?
- Chaperone for proper folding of Class II MHC molecules
- Prevent binding by endogenous peptides while in ER
- Traffics Class II MHC to endosomal pathway where peptides can be loaded in vesicle where pathogen was killed (phagolysosome)
What is the function of HLA-DM in the presentation of exogenous antigens?
Removes the CLIP and facilitates peptide loading
What are the roles/functions of TAP, tapasin, and calnexin in the presentation of endogenous antigens?
- TAP moves peptides to the ER (using ATP)
- Calnexin stabilizes MHC class I in the ER. Also prevents premature exit of an unloaded class I molecule in the ER
- Tapasin moves TAP and Calnexin closer together to facilitate peptide loading
Is β2 macroglobulin polymorphic?
No it is invariant ie never changes
MHC molecules are polymorphic
What is meant by promiscuous binding?
Each MHC molecule is capable of dining many different antigenic peptides (reason for this: 1000s of antigenic peptides)
What is the function of the invariant chain in the presentation of exogenous antigens?
- Chaperone for proper folding of Class II MHC molecules
- Prevent binding by endogenous peptides while in ER
- Traffics Class II MHC to endosomal pathway where peptides can be loaded in vesicle where pathogen was killed (phagolysosome)
What is the function of HLA-DM in the presentation of exogenous antigens?
Removes the CLIP and facilitates peptide loading
What are the roles/functions of TAP, tapasin, and calnexin in the presentation of endogenous antigens?
- TAP moves peptides to the ER (using ATP)
- Calnexin stabilizes MHC class I in the ER. Also prevents premature exit of an unloaded class I molecule in the ER
- Tapasin moves TAP and Calnexin closer together to facilitate peptide loading
Is β2 macroglobulin polymorphic?
No it is invariant ie never changes
MHC molecules are polymorphic
What is meant by promiscuous binding?
Each MHC molecule is capable of dining many different antigenic peptides (reason for this: 1000s of antigenic peptides)
What is the function of the invariant chain in the presentation of exogenous antigens?
- Chaperone for proper folding of Class II MHC molecules
- Prevent binding by endogenous peptides while in ER
- Traffics Class II MHC to endosomal pathway where peptides can be loaded in vesicle where pathogen was killed (phagolysosome)
What is the function of HLA-DM in the presentation of exogenous antigens?
Removes the CLIP and facilitates peptide loading
What are the roles/functions of TAP, tapasin, and calnexin in the presentation of endogenous antigens?
- TAP moves peptides to the ER (using ATP)
- Calnexin stabilizes MHC class I in the ER. Also prevents premature exit of an unloaded class I molecule in the ER
- Tapasin moves TAP and Calnexin closer together to facilitate peptide loading
Is β2 macroglobulin polymorphic?
No it is invariant ie never changes
MHC molecules are polymorphic
What is meant by promiscuous binding?
Each MHC molecule is capable of dining many different antigenic peptides (reason for this: 1000s of antigenic peptides)
What is the function of the invariant chain in the presentation of exogenous antigens?
- Chaperone for proper folding of Class II MHC molecules
- Prevent binding by endogenous peptides while in ER
- Traffics Class II MHC to endosomal pathway where peptides can be loaded in vesicle where pathogen was killed (phagolysosome)
What is the function of HLA-DM in the presentation of exogenous antigens?
Removes the CLIP and facilitates peptide loading
What are the roles/functions of TAP, tapasin, and calnexin in the presentation of endogenous antigens?
- TAP moves peptides to the ER (using ATP)
- Calnexin stabilizes MHC class I in the ER. Also prevents premature exit of an unloaded class I molecule in the ER
- Tapasin moves TAP and Calnexin closer together to facilitate peptide loading
Is β2 macroglobulin polymorphic?
No it is invariant ie never changes
MHC molecules are polymorphic
What is meant by promiscuous binding?
Each MHC molecule is capable of dining many different antigenic peptides (reason for this: 1000s of antigenic peptides)
What is the function of the invariant chain in the presentation of exogenous antigens?
- Chaperone for proper folding of Class II MHC molecules
- Prevent binding by endogenous peptides while in ER
- Traffics Class II MHC to endosomal pathway where peptides can be loaded in vesicle where pathogen was killed (phagolysosome)
What is the function of HLA-DM in the presentation of exogenous antigens?
Removes the CLIP and facilitates peptide loading
What are the roles/functions of TAP, tapasin, and calnexin in the presentation of endogenous antigens?
- TAP moves peptides to the ER (using ATP)
- Calnexin stabilizes MHC class I in the ER. Also prevents premature exit of an unloaded class I molecule in the ER
- Tapasin moves TAP and Calnexin closer together to facilitate peptide loading
Is β2 macroglobulin polymorphic?
No it is invariant ie never changes
MHC molecules are polymorphic
What is meant by promiscuous binding?
Each MHC molecule is capable of dining many different antigenic peptides (reason for this: 1000s of antigenic peptides)
What is the function of the invariant chain in the presentation of exogenous antigens?
- Chaperone for proper folding of Class II MHC molecules
- Prevent binding by endogenous peptides while in ER
- Traffics Class II MHC to endosomal pathway where peptides can be loaded in vesicle where pathogen was killed (phagolysosome)
What is the function of HLA-DM in the presentation of exogenous antigens?
Removes the CLIP and facilitates peptide loading
What are the roles/functions of TAP, tapasin, and calnexin in the presentation of endogenous antigens?
- TAP moves peptides to the ER (using ATP)
- Calnexin stabilizes MHC class I in the ER. Also prevents premature exit of an unloaded class I molecule in the ER
- Tapasin moves TAP and Calnexin closer together to facilitate peptide loading
Is β2 macroglobulin polymorphic?
No it is invariant ie never changes
MHC molecules are polymorphic
What is meant by promiscuous binding?
Each MHC molecule is capable of dining many different antigenic peptides (reason for this: 1000s of antigenic peptides)
What is the function of the invariant chain in the presentation of exogenous antigens?
- Chaperone for proper folding of Class II MHC molecules
- Prevent binding by endogenous peptides while in ER
- Traffics Class II MHC to endosomal pathway where peptides can be loaded in vesicle where pathogen was killed (phagolysosome)
What is the function of HLA-DM in the presentation of exogenous antigens?
Removes the CLIP and facilitates peptide loading
What are the roles/functions of TAP, tapasin, and calnexin in the presentation of endogenous antigens?
- TAP moves peptides to the ER (using ATP)
- Calnexin stabilizes MHC class I in the ER. Also prevents premature exit of an unloaded class I molecule in the ER
- Tapasin moves TAP and Calnexin closer together to facilitate peptide loading
Is β2 macroglobulin polymorphic?
No it is invariant ie never changes
MHC molecules are polymorphic
What is meant by promiscuous binding?
Each MHC molecule is capable of dining many different antigenic peptides (reason for this: 1000s of antigenic peptides)
What is the function of the invariant chain in the presentation of exogenous antigens?
- Chaperone for proper folding of Class II MHC molecules
- Prevent binding by endogenous peptides while in ER
- Traffics Class II MHC to endosomal pathway where peptides can be loaded in vesicle where pathogen was killed (phagolysosome)
What is the function of HLA-DM in the presentation of exogenous antigens?
Removes the CLIP and facilitates peptide loading
What are the roles/functions of TAP, tapasin, and calnexin in the presentation of endogenous antigens?
- TAP moves peptides to the ER (using ATP)
- Calnexin stabilizes MHC class I in the ER. Also prevents premature exit of an unloaded class I molecule in the ER
- Tapasin moves TAP and Calnexin closer together to facilitate peptide loading
Is β2 macroglobulin polymorphic?
No it is invariant ie never changes
MHC molecules are polymorphic
What is meant by promiscuous binding?
Each MHC molecule is capable of dining many different antigenic peptides (reason for this: 1000s of antigenic peptides)
What is the function of the invariant chain in the presentation of exogenous antigens?
- Chaperone for proper folding of Class II MHC molecules
- Prevent binding by endogenous peptides while in ER
- Traffics Class II MHC to endosomal pathway where peptides can be loaded in vesicle where pathogen was killed (phagolysosome)
What is the function of HLA-DM in the presentation of exogenous antigens?
Removes the CLIP and facilitates peptide loading
What are the roles/functions of TAP, tapasin, and calnexin in the presentation of endogenous antigens?
- TAP moves peptides to the ER (using ATP)
- Calnexin stabilizes MHC class I in the ER. Also prevents premature exit of an unloaded class I molecule in the ER
- Tapasin moves TAP and Calnexin closer together to facilitate peptide loading
Is β2 macroglobulin polymorphic?
No it is invariant ie never changes
MHC molecules are polymorphic
What is meant by promiscuous binding?
Each MHC molecule is capable of dining many different antigenic peptides (reason for this: 1000s of antigenic peptides)
What is the function of the invariant chain in the presentation of exogenous antigens?
- Chaperone for proper folding of Class II MHC molecules
- Prevent binding by endogenous peptides while in ER
- Traffics Class II MHC to endosomal pathway where peptides can be loaded in vesicle where pathogen was killed (phagolysosome)
What is the function of HLA-DM in the presentation of exogenous antigens?
Removes the CLIP and facilitates peptide loading
What are the roles/functions of TAP, tapasin, and calnexin in the presentation of endogenous antigens?
- TAP moves peptides to the ER (using ATP)
- Calnexin stabilizes MHC class I in the ER. Also prevents premature exit of an unloaded class I molecule in the ER
- Tapasin moves TAP and Calnexin closer together to facilitate peptide loading
Is β2 macroglobulin polymorphic?
No it is invariant ie never changes
MHC molecules are polymorphic
What is meant by promiscuous binding?
Each MHC molecule is capable of dining many different antigenic peptides (reason for this: 1000s of antigenic peptides)
What is the function of the invariant chain in the presentation of exogenous antigens?
- Chaperone for proper folding of Class II MHC molecules
- Prevent binding by endogenous peptides while in ER
- Traffics Class II MHC to endosomal pathway where peptides can be loaded in vesicle where pathogen was killed (phagolysosome)
What is the function of HLA-DM in the presentation of exogenous antigens?
Removes the CLIP and facilitates peptide loading
What are the roles/functions of TAP, tapasin, and calnexin in the presentation of endogenous antigens?
- TAP moves peptides to the ER (using ATP)
- Calnexin stabilizes MHC class I in the ER. Also prevents premature exit of an unloaded class I molecule in the ER
- Tapasin moves TAP and Calnexin closer together to facilitate peptide loading
Is β2 macroglobulin polymorphic?
No it is invariant ie never changes
MHC molecules are polymorphic
What is meant by promiscuous binding?
Each MHC molecule is capable of dining many different antigenic peptides (reason for this: 1000s of antigenic peptides)
What is the function of the invariant chain in the presentation of exogenous antigens?
- Chaperone for proper folding of Class II MHC molecules
- Prevent binding by endogenous peptides while in ER
- Traffics Class II MHC to endosomal pathway where peptides can be loaded in vesicle where pathogen was killed (phagolysosome)
What is the function of HLA-DM in the presentation of exogenous antigens?
Removes the CLIP and facilitates peptide loading
What are the roles/functions of TAP, tapasin, and calnexin in the presentation of endogenous antigens?
- TAP moves peptides to the ER (using ATP)
- Calnexin stabilizes MHC class I in the ER. Also prevents premature exit of an unloaded class I molecule in the ER
- Tapasin moves TAP and Calnexin closer together to facilitate peptide loading
Is β2 macroglobulin polymorphic?
No it is invariant ie never changes
MHC molecules are polymorphic
What is meant by promiscuous binding?
Each MHC molecule is capable of dining many different antigenic peptides (reason for this: 1000s of antigenic peptides)
What is the function of the invariant chain in the presentation of exogenous antigens?
- Chaperone for proper folding of Class II MHC molecules
- Prevent binding by endogenous peptides while in ER
- Traffics Class II MHC to endosomal pathway where peptides can be loaded in vesicle where pathogen was killed (phagolysosome)
What is the function of HLA-DM in the presentation of exogenous antigens?
Removes the CLIP and facilitates peptide loading
What are the roles/functions of TAP, tapasin, and calnexin in the presentation of endogenous antigens?
- TAP moves peptides to the ER (using ATP)
- Calnexin stabilizes MHC class I in the ER. Also prevents premature exit of an unloaded class I molecule in the ER
- Tapasin moves TAP and Calnexin closer together to facilitate peptide loading
Is β2 macroglobulin polymorphic?
No it is invariant ie never changes
MHC molecules are polymorphic
What is meant by promiscuous binding?
Each MHC molecule is capable of dining many different antigenic peptides (reason for this: 1000s of antigenic peptides)
What is the function of the invariant chain in the presentation of exogenous antigens?
- Chaperone for proper folding of Class II MHC molecules
- Prevent binding by endogenous peptides while in ER
- Traffics Class II MHC to endosomal pathway where peptides can be loaded in vesicle where pathogen was killed (phagolysosome)
What is the function of HLA-DM in the presentation of exogenous antigens?
Removes the CLIP and facilitates peptide loading
What are the roles/functions of TAP, tapasin, and calnexin in the presentation of endogenous antigens?
- TAP moves peptides to the ER (using ATP)
- Calnexin stabilizes MHC class I in the ER. Also prevents premature exit of an unloaded class I molecule in the ER
- Tapasin moves TAP and Calnexin closer together to facilitate peptide loading
Is β2 macroglobulin polymorphic?
No it is invariant ie never changes
MHC molecules are polymorphic
What is meant by promiscuous binding?
Each MHC molecule is capable of dining many different antigenic peptides (reason for this: 1000s of antigenic peptides)
What is the function of the invariant chain in the presentation of exogenous antigens?
- Chaperone for proper folding of Class II MHC molecules
- Prevent binding by endogenous peptides while in ER
- Traffics Class II MHC to endosomal pathway where peptides can be loaded in vesicle where pathogen was killed (phagolysosome)
What is the function of HLA-DM in the presentation of exogenous antigens?
Removes the CLIP and facilitates peptide loading
What are the roles/functions of TAP, tapasin, and calnexin in the presentation of endogenous antigens?
- TAP moves peptides to the ER (using ATP)
- Calnexin stabilizes MHC class I in the ER. Also prevents premature exit of an unloaded class I molecule in the ER
- Tapasin moves TAP and Calnexin closer together to facilitate peptide loading
Is β2 macroglobulin polymorphic?
No it is invariant ie never changes
MHC molecules are polymorphic
What is meant by promiscuous binding?
Each MHC molecule is capable of dining many different antigenic peptides (reason for this: 1000s of antigenic peptides)
What is the function of the invariant chain in the presentation of exogenous antigens?
- Chaperone for proper folding of Class II MHC molecules
- Prevent binding by endogenous peptides while in ER
- Traffics Class II MHC to endosomal pathway where peptides can be loaded in vesicle where pathogen was killed (phagolysosome)
What is the function of HLA-DM in the presentation of exogenous antigens?
Removes the CLIP and facilitates peptide loading
What are the roles/functions of TAP, tapasin, and calnexin in the presentation of endogenous antigens?
- TAP moves peptides to the ER (using ATP)
- Calnexin stabilizes MHC class I in the ER. Also prevents premature exit of an unloaded class I molecule in the ER
- Tapasin moves TAP and Calnexin closer together to facilitate peptide loading
Is β2 macroglobulin polymorphic?
No it is invariant ie never changes
MHC molecules are polymorphic
What is meant by promiscuous binding?
Each MHC molecule is capable of dining many different antigenic peptides (reason for this: 1000s of antigenic peptides)
What is the function of the invariant chain in the presentation of exogenous antigens?
- Chaperone for proper folding of Class II MHC molecules
- Prevent binding by endogenous peptides while in ER
- Traffics Class II MHC to endosomal pathway where peptides can be loaded in vesicle where pathogen was killed (phagolysosome)
What is the function of HLA-DM in the presentation of exogenous antigens?
Removes the CLIP and facilitates peptide loading
What are the roles/functions of TAP, tapasin, and calnexin in the presentation of endogenous antigens?
- TAP moves peptides to the ER (using ATP)
- Calnexin stabilizes MHC class I in the ER. Also prevents premature exit of an unloaded class I molecule in the ER
- Tapasin moves TAP and Calnexin closer together to facilitate peptide loading
Is β2 macroglobulin polymorphic?
No it is invariant ie never changes
MHC molecules are polymorphic
What is meant by promiscuous binding?
Each MHC molecule is capable of dining many different antigenic peptides (reason for this: 1000s of antigenic peptides)
What is the function of the invariant chain in the presentation of exogenous antigens?
- Chaperone for proper folding of Class II MHC molecules
- Prevent binding by endogenous peptides while in ER
- Traffics Class II MHC to endosomal pathway where peptides can be loaded in vesicle where pathogen was killed (phagolysosome)
What is the function of HLA-DM in the presentation of exogenous antigens?
Removes the CLIP and facilitates peptide loading
What are the roles/functions of TAP, tapasin, and calnexin in the presentation of endogenous antigens?
- TAP moves peptides to the ER (using ATP)
- Calnexin stabilizes MHC class I in the ER. Also prevents premature exit of an unloaded class I molecule in the ER
- Tapasin moves TAP and Calnexin closer together to facilitate peptide loading
