Lecture 9: MHC and Antigen Presentation Flashcards
Antigen processing
Generation of peptides from proteins
Antigen presentation
Display of processed peptide on cell surface via MHC molecules
What are the three types of professional APC’s
Dendritic cells, macrophages and B cells
What do MHC I molecules present on
All nucleated cells
What do MHC II molecules present on
Antigen presenting cells
What type of T cell do dendritic cells present to and what is the response
Naive T cells and results in clonal differentiation and proliferation of effector T cells
What type of T cell do macrophages present to and what is the response
Present to effector T cells and results in activation of macrophages- cell mediated immunity
What type of T cells do B cells present to and what is the response
Present to effector T cells and result in B cell activation and antibody production-humoral immunity
Where are cytosolic pathogens degraded
Cytosol
What do cytosolic pathogens bind to
MHC I
What are cytosolic presented to
CD8+ T cells
What is the effect of presenting cytosolic pathogens to CD8+ T cells
Cell death
What are intravesicular pathogens
Pathogens that can survive and replicate inside a phagosome and/or phagolysosome
Where are intravesicular pathogens degraded
Endocytotic vesicles with low PH
What do intravesicular pathogens bind to
MHC II
Where are intravesicular pathogens presented
CD4+ T cells
What is the effect of presenting intravesicular pathogens to CD4+ T cells
Activation to kill intravesicular bacteria
What are extracellular pathogens
Bacteria growing outside of cell, viruses not yet in target cell. They can be bound by BCR and endocytosed
Where are extracellular pathogens degraded
Endocytotic vesicle with low Ph
What do extracellular pathogens bind to
MHC II
Where are extracellular pathogens presented
CD4+ T cells
What is the effect on presenting extracellular pathogens to CD4+ T cells
Activation of B cells to secrete Ig to eliminate bacteria/toxins
What is the messenger between innate and adaptive immunity
Dendritic cell
How do dendritic cells sample environment
TLR’s
When dendritic cells bind an antigen what is unregulated and for what purpose
Upregulate CD molecules to initiate T cell binding- differentiates CD8+-Tc and CD4+-Th
What are the variable regions on MHC I molecule
Alpha-1 and alpha-2
What are the components of MHC I structure
Alpha-1, alpha-2, B2-microglobulin
Where are the variable regions on MHC II
Beta-1
What is the structure of MHC II molecule
Alpha-1, alpha-2, beta-1, beta-2
All MHC molecules must be bound to a peptide to be ______
Expressed on the cell surface, when not bound will be broken down empty MHC molecule not on surface
Any ___ processed into a peptide can bind into the ____ and be presented to a T cell
Any protein- self or non-self
MHC groove
MHC restricted T cells respond mainly to lipids, carbohydrates, sugars, or proteins
Proteins broken down into peptides
If T cell binds high affinity with MHC + peptide then what happens
T cell activation
What type of peptides do MHC I molecules bind and what type of T cell do they present to
Bind endogenous peptides and present to CD8+ T cells
What type of peptides do MHC II molecules bind and what type of T cell do they present to
exogenous and CD4+ T cells
Where are MHC I molecules translated to and fold
ER, they don’t see antigens in cytosol
What protein is responsible for carrying in amino acid strands to MHC I
Transporter proteins (TAP)
What is a proteasome
Degrades proteins into peptides
What increases the rate of proteolysis
INF-gamma
The increase rate of proteolysis ____likelihood that antigenic peptides escape this processing
Increases
___transports peptides to TAP
Chaperones
Describe the steps in the MHC I Antigenic Peptide Generation
Partly folded MHC I alpha chain will bind calnexin while waiting for B2m
Alpha-B2m binds and releases calnexin and binds chaperones and TAP via tapasin
Cytosolic proteins and defective ribosomal products are degraded into peptides via proteasome. TAP delivers peptides to ER
Peptide binds MHC and completes folding, MHC is released from TAP and exported to cell membrane
What are immunoevasins
Allow viruses to evade antigen presentation by blocking TAP functions, block antigenic peptide loading into MHC, can tag MHC molecules for degradation
What do US6 and ICP47 do
They are immunoevasins that block TAP and prevent antigen from moving from cytosol to ER to bind MHC
What is adenovirus protein E19
Immunoevasins that disrupts tapasin binding to MHC molecule and inhibits antigenic peptide loading
What is Mk3
E3-ubiquitin ligase that targets MHC I for degradation
What are some examples of organisms that replicate in vesicles in macrophages
Leishmania, mycobacterium and salmonella
What are intravesicular bacteria not exposed to and what must then degrade proteins
Cytosolic proteasome so intravesicular proteases degrade proteins
Describe steps of MHCII and intravesicular bacteria
Antigen is taken up from extracellular space into intravesicular vesicle
In early endosomes pH is neutral so proteases are inactive
Acidification of vesicles activates proteases to degrease peptides to proteins
Vesicles containing peptide fuse with vesicle containing MHC II
What does the invariant chain prevent
Binding to self antigens
Describe the steps of MHC II antigenic prep for endocytosed/BCR bound antigens
Invariant chain forms complex with MHC blocking binding of self peptides, misfolded proteins
Invariant chain is cleaved in acidified endosome and leaves short peptide called CLIP bound to MHC.
Endocytosed antigens are degrade into peptides but CLIP is still blocking their binding to MHC
HLA-DM binds to MHC II releasing CLIP and allowing other peptides to bind MHC II. MHC II then travels to cell surface
What is the role of HLA-DM and where is it found
Role: catalyzes loading of antigen into MHCII binding pocket
Found: only in MHC II compartment
Cross presentation and activation of naive CD8 T cells
Some dendritic cells present on their MHC I molecules
What is the source of protein antigens in MHC II pathway?
Endosomal/lysosomal proteins- internalized from extracellular environment
What is the source of protein antigens in MHC I pathway
Cytosolic proteins- mostly synthesized in cell
What are the enzymes responsible for peptide generation in MHC II pathway
Endosomal and lysosomal proteases
What enzymes are responsible for peptide generation in MHC I
Enzymatic components of cytosolic proteasome
What is the site of peptide loading of MHC II pathway
Late endosomes and lysosomes
What is the site of peptide loading in MHC I
Endoplasmic reticulum
What molecules are involved in transport of peptides and loading of MHC molecules in MHC II pathway
Invariant chain and HLA-DM
What molecules are involved in transport of peptides and loading of MHC molecules in MHC I pathway
TAP
How are MHCs able to bind so many antigens
Genetic diversity with many different loci
What are the loci in MHC I and what do they encode for
HLA-A, B, C and encode for alpha chain
What are the loci in MHC II and what do they encode for
HLA-DP, DQ, DR and encode for alpha and beta chains
Polymorphic
Multiple alleles for each gene
What is a HLA haplotype
Set of MHC alleles present on each chromosome
Each person has __ HLA haplotypes
2
Professional APC’s expresses alleles of which class (es)
MHC I and II
All nucleated cells express which class (es)
MHC I
The diversity of MHC alleles expressed partially determines individuals susceptibility to _____
Infectious diseases
Is it advantageous to be MHC heterozygote or homozygote
Heterozygote can respond to greater number of antigens
There has been linkage between expression of certain DLA haplotypes and susceptibility to what diseases
Canine RA, I-M hemolytic anemiadiabetes mellitus
Association between expression of certain BoLA alleles and resistance to what has been shown
Resistant to bovine leukosis due to infection with bovine leukemia virus
What are superantigens
Toxins that encourage the aberrant binding of MHC and TCR results in long lived binding and cytokine storm
