(06) MHC Flashcards
T or F: MHC plays a big role in transplant rejection
True
MHC
- what chromosome?
- What macromolecules make it up?
- Chromosome 6
- Glycoproteins
What binds MHC?
T cells bind after the MHC presents the PEPTIDE
MHC class I structure:
- Subunits
- functional parts
- encoding
Overall - Heterodimer
Alpha 1 and 2
- Creates binding cleft
Alpha 3
- contains transmembrane domain
Beta 2
- Not encoded in the the MHC complex
MHC Class II structure:
- Subunits
- Functional Parts
- encoding
Overall - Heterodimer
Alpha 1 and Beta 1
- binding domains
Alpha 2 and Beta 2
- transmembrane domains
**All are encoded at the MHC locus
Why are MHC molecules able to present all 10^18 peptides that T cell receptors can recognize?
- They binding in a promiscuous fashion, MUCH LESS SPECIFICITY
How big are the peptide fragments presented by MHC class I? - what determines this cut-off?
- 8-10 amino acids long
- Bound peptide interacts with the edges of the binding pocket that contains invariant contacts with the N and C terminal ends of the peptide
What are anchor residues in MHC class I?
- residues (usually 2?) that will be constant among one persons group of MHC class I’s, however they will vary from person to person (polygenics, and polymorphism)
How do the binding chacteristics of MHC class I vary form MHC class II?
MHC class II:
- must be AT LEAST 13 amino acids long
- Edges do not limit binding cleft
MHC class I:
- must be NO MORE than 8-10 residues
- Edges limit binding cleft
For what reason are MHC complexes so promiscuous?
- binding pockets only require that 2-4 residues fall into a certain structural category of amino acids
T or F: MHC plays a vital role in telling the body whether its dealing with an intracellular infection or extracellular infection
True
How does the body use MHCs to determine where the pathogen lives?
MHC class I - Processing and presentation of INTRACELLULAR pathogens
MHC class II - Processing and presentation of EXTRACELLULAR pathogens
What is the MHC class I pathway? - what type of pathogen does this protect against?
Takes place IN the ER.
- MHC Class I is stabilized by Calnexin
- MHC Class I binds to Protein Loading complex and TAP
- TAP imports peptide fragments and PLP loads them to MHC
- MHC with bound peptide is exprelled to golgi then to cell surface
Suppose you have a patient who presents with very little MHC class I on their cells, yet their MHC class one gene is perfectly functional. why is this?
TAP1/2 genes could be defective. - it presents this way because MHC class I is very unstable without being bound to peptides
When is the MHC class I pathways occurring? - what are some possible reactions to presentation of antigen?
- All of the time
Possible Outcomes:
- Nothing happens because the peptide is normal
- Abnormal peptide is presented on APC and Naive T Cells are notified
- Abnormal peptide is presented on regular cell and cytotoxic T-cells kill it
In general how does the MHC class II pathways work?
- Extracellular Mileu is sampled and MHC class II is sent back out with parts of it
MHC class II
- where is it found?
- What type of proteins does it bind?
- ONLY antigen presenting cells
- Binds BOTH host and pathogenic cells so MAJORITY of BOUND PROTEINS are HOST proteins
- T cells must differentiate what’s pathogenic and what isn’t
MHC class II - pathway
- MHC class II resides in ER bound to INVARIANT CHAIN
- MHC II vesicle Buds off then goes to golgi and invariant chain is degraded leaving CLIP behind in the binding cleft
- MHC class II binds to phagosome and HLA-DM dislodges CLIP and TProtein is bound
- MHC class II vesicle continues and combines with cell membrane
T or F: there is some crossover between proteins loaded on MHC I and MHC II
True, the pathways are not 100% exclusive
What is the only tissue to lack MHC I expression?
- why is this?
Erythrocytes
- T cells can’t kill enucleate cells
Explain why MHC I levels are the way they are on the:
- Liver
- Kidney
- Brain
Low on these tissues because killing cells that are essential for survival is pointless
Especially Low in the Liver
Where can you find MHC II expression in the greatest proportions?
APCs:
- Macrophages
- Dendritic Cells
- B cells
Thymic Epithelium
What is the difference in the type of T cell that is recruited by MHC class I and MHC class II?
MHC class I - presents to CD8
MHC class II - presents to CD4
What players are involved in the extracellular response?
MHC class II —> CD4 —> antibodies
**CD4 is critical for linking the extracellular sensory system with the extracellular response
What is polygeny?
- what is an immune system example?
- 2 or more proteins with similar structure having similar (identical) function existing at 2 Different parts of the genome
- MHC I and MHC II
What is polymorphism?
- what is an immune system example?
- 2 or more varients of a gene in a population (alleles)
- MHC I and MHC II
T or F: there is a tremendous clinical relevance for MHC class I and MHC class II being both polymorphic and polygenic.
True
Polygenic Nature MHC class I and MHC Class two
3 loci encode for MHC class I isoforms
- HLA-A
- HLA-B
- HLA-C
3 loci encode for MHC class II isoforms that WITHIN THEM have code for alpha and beta chains
- HLA-DP
- HLA-DQ
- HLA-DR (can have 2 two different genes) ***
Polymorphic Nature of the MHC genes
**each of the Loci for all MHC genes are super polymorphic (different individuals are likely to have different versions of the gene)
**Most polymorphic genes in the genome
Where (in sequence) are most polymorphisms in MHC genes found?
in sequence that codes for the binding region of MHC molecules
- This is why the binding regions are variable from person to person.
What is the largest and smallest number of different isotypes a person can express of MHC class I? - is the a result of polygenics or polymorphisms?
3 (homozygote)-6 isotypes possible on all nucleated cells
- Polygenic
(variation from person to person = polymorphism)
MHC class two
- minimum number of isotypes
- why
3 - 16
*greater number has to do with alpha and beta chains within genes expressing individual polymorphisms and being able to mix
Is it better to inherit express the minimum or maximum amounts of isotypes?
- why
There are benefits to both:
- Minimum number of isotypes –> you will be more likely to be able to accept an implant
- Maximum number of isotypes
- -> you will probably be a little more immunologically protected
What is the basic of transplant rejection?
MHC molecules of the host don’t match those of the organ donor
Differentiate between transplant types
- syngeneic (isograft)
- allogeneic (allograft)
- zenograft
Isograft
- genetically identical individuals
Allogeneic
- genetically distinct individuals
zenograft
- different species
