MHC Complexes Flashcards
Give a brief description of the MHC I molecules
Member of the Ig superfamily
Three external domains, one transmembrane domain (alpha) beta microglobulin protein.
Cytoplasmic anchor
Alpha 1 and 2 domains form cleft region that binds 8-10 AA peptide fragment from Ag (Cleft is made by two sandwiching alpha helixes and a beta sheet bottom.
Where does MHC I exhibit polymorphism?
Peptide binding region.
Describe the peptide binding region of the MHC I.
Binding betweel alpha1/2, closed at both ends limits AA to 8-10. Some AAs anchor peptide others interact with TcR
Define MHC promiscuity.
Can bind to numerous different peptides.
The MHC is aka _____
Where is this found in our genetics?
The MHC locus encodes for which classes of molecules?
Human leukocyte Ag complex - HLA
Chromosome 6
Class I, II, and III
The MHC complex is the more _____ region in the entire genome.
Polymorphic
How are MHCs inherited? What is the genetic expression of MHC?
In linked groups called haplotypes.
One haplotype from mom and one from dad are CODOMINANT.
How does MHC diversity affect our immune systems?
Provides flexibility in responding to unexpected environmental changes now and in the future. Certain people may be able to respond better than others to the same threat.
Which HLA is the major presenter of peptides?
HLA-B
Describe the genetic diversity among ethnic groups around the world of HLAs.
HLA-B, the major peptide presenter, varies widely around the world based on the different threats they may encounter in those areas of the world.
Describe the different MHC loci in different species.
How many unique classical MHC I molecules per cell?
Organization of MHC loci differs between species - polygenic diversity is different.
Human have 6 (2 each of Class I, II, and III)
What does MHC I present? Why?
Where is MHC I expression found?
To whom does MHC I present?
Intracellular Ag peptides Self proteins, viral infections, abnormal cells like cancer To check that cells are healthy. MHC I in all nucleated cells. To CD8+ T cells
Describe how MHC expression can change with the conditions?
Proteasome recycles defective ribosomal products. Genetic/cell regulatory cycles can drive up/down MHC expression and so can cytokines. Viruses can shut down MHC to avoid detection.
Briefly describe HLA-G
Non-classical MHC I molecule. Similar to HLA class I - does not bind TcR and interacts with inhibitory receptors.
What is the function of HLA-G
It is a tolerogenic molecule with limited protein variability. It has several isoforms.
Unique molecular structure with reduced cytoplasmic tail.
It modulates the immune response.
Where is HLA-G expression?
Placental tissues and tumours.
Briefly describe the MHC II molecules
Member of Ig superfamily
Heterodimeric with alpha and beta chains which both pass through membrane.
Binding cleft formed by alpha/beta 1 domains
Accommodates peptides of 13-18 AAs
Define motif
Common sequence in peptide Ag that binds MHC molecule
Define anchor residues.
AAs anchor peptide to MHC groove
Describe the MHC II binding cleft for peptides.
Open ended which allows 13-18 AA lengths
Why are MHC polymorphisms important in terms of pathogens?
Pathogens will always reproduce and mutate faster than humans will so the MHC polymorphisms counteract this.
Humans must have variants of each type of MHC molecule and the population must be very varied to protect from extinction.
How can HLA alleles influence medical treatment?
They can be used to deal with personalized medicine. Some HLA alleles slow or accelerate different illnesses and if they are genotyped the physician can better understand how to treat the individual.
Contrast the differences between MHCs and T/Bcells.
MHC molecules do not vary within the lifetime of an individual and there is a high diversity of variants at the population level.
T/B cells receptors are inconstant flux within an individual though they are roughly the same through out populations
Briefly discuss the MHC polymorphisms and mate choosing.
People are more likely to choose mates based on their MHC differences ensuring their offspring will have better immune systems.
Briefly describe MHC II Ag processing.
Where is it expressed?
To whom does MHC II present?
Presents extracellular peptides (pathogens).
Usually only on APCs
CD4+ T cells
What are HLA-DM and HLA-DO?
HLA-DM: regulates loading of MHC II molecules to catalyze peptide exchange.
HLA-DO: acts as substrate mimic to inhibit HLA-DM mediated catalysis of MHC peptide exchange.
— DO uses CLIP to bind to avoid other peptides being presented. DM binds to MHC when viral peptides are available and then CLIP is released and MHC goes to surface.
