Sara - MHC Binding, Polymorphism and Processing Flashcards
How many different Class I molecules can an individual express?
Up to 6 different types
How many different Class II molecules can an individual express?
12
Describe the peptide binding to MHC
(4)
It is not highly specific
Unlike antibodies or T cell receptors
The MHC must be able to present a huge array of antigens to T cells
MHC undergoes promiscuous binding
What is meant by promiscuous binding
The ability of MHC to bind multiple different antigens and present them to T cells
What is the ideal length of a peptide for Class I?
9 amino acids long (between 8 and 10)
What happens if a longer peptide binds to the groove of MHC Class I?
It can be cleaved in the endoplasmic reticulum by exopeptidases
Give an example of an exopeptidase
ERAp
Give an example of an exopeptidase
ERAP
What does the MHC peptide require during peptide binding?
The peptide must contain specific amino acid residues:
- at the amino and carboxy termini
- at positions 2 and or 3 and 9
What does histocompatibility determine?
Determines whether cells in a tissue are seen as self or not
What is the region that codes for MHC in mice called?
The H2 region
What does MHC class III do?
(2)
Produces TNFa
Produces heat shock proteins
How many Class I molecules can be produced from a chromosome 6?
Three class I molecules
What must be done to antigens in order for MHC to use them?
The antigens must be processed into peptides -> between 8 and 10 amino acids long for Class I
What type of peptide fragments are generally used for Class I?
Endogenous peptide fragments
What type of peptide fragment are generally used for Class II?
Exogenous peptides
What is meant by an endogenous peptide and how are they processed?
(4)
A viral peptide -> virus uses cell’s biological machinery to make it’s viral proteins inside (endogenous) the cell
Immunoproteosome enzymic subunits breaks these proteins down into peptides
Transporter associated with antigen processing (TAP) shuttles peptides to ER
MHC complex made and sent to cell surface via golgi apparatus
Where does MHC loading take place?
In the Endoplasmic reticulum
What is meant by exogenous peptides and how are they loaded into MHC Class II?
(4)
APC engulfs a bacteria (exogenous)
Phagosome and lysosome = phagolysosome
Bacterial peptides brought to ER for loading
MHC Class II expressed on surface of APC
Name the alleles that code for MHC alpha chain
B, C and A
What is the cytosolic pathway of antigen processing
The loading of MHC Class I molecules with endogenous peptides
In the endogenous pathway of antigen presentation in MHC Class I, what breaks down viral peptides?
Immunoproteosome enzymic subunits breaks these proteins down into peptides
What does TAP stand for?
Transporter associated with antigen processing
How is the immunoproteasome shaped?
Barrel shaped
How can B cells undergo antigen presentation?
Via receptor mediated endocytosis (not phagocytosis)
During the processing stage, what is the main difference between the endogenous and exogenous presentation of peptides?
In the exogenous pathway, after phagocytosis/endocytosis the MHC Class II is sent to the membrane bound vesicle containing the peptide (CD74 tells the MHC where to go)
List the three MHC Class I molecules
HLA-B, HLA-C, HLA-A
Where do the alpha and beta chains of MHC Class II come form?
Coded by alleles on the short arm of chromosome 6 (other end to the MHC Class I)
Describe the alleles that code for MHC Class II a and B chains?
They are both polymorphic genes (unlike MHC Class I)
How many regions are there to the alpha chain of MHC Class I?
2 regions (a1, a2)
How many regions are there to the B chain of the MHC Class II?
Two regions (B1, B2)
What is the preferred peptide size for MHC Class II?
13-18 amino acids
Why can only some cells express MHC Class II?
(3)
MHC Class II presents antigens to Helper T cells (CD4+)
Helper T cells are responsible for releasing a lot of cytokines to trigger other cells
If all cells could express MHC Class II we would have a cytokine storm and die
What are the three alleles that code for the alpha and beta chains of MHC Class II?
DB, DQ, DR (each of these loci code for an alpha and a beta chain)
How many class II molecules can you have?
12
