Lecture 16 - Linking Innate & Adaptive Immunity (Exceptions and MHC Genetics) Flashcards
What are the three exceptions to standard pMHC-TCR activation of T-cells?
Cross-Presentation, Presentation of Cytosolic Peptides by MHCII, and Allorecognition
What is cross-presentation? How does this occur?
Cross-presentation is when DCs redirect exogenous antigens to the endogenous presentation pathway. It is unclear how this actually happens, but DCs may need a “license” obtained by presenting foreign antigen to CD4+ T-cells that acts as a back/forth cytokine signal between the APC and T-cell.
How can cross-presentation switch a DC from presenting Ag to CD4+ T-cells to CD8+ T-cells?
When the DC processes the exogenous Ag using the endogenous pathway, it causes the pMHC complex to be made using MHCI, not MHCII. As such, the pMHCI complex will go onto triggering CD8+ T-cells instead of CD4+ T-cells like it would have if processed using the exogenous pathway.
How does presentation of cytosolic peptides by MHCII occur?
This occurs via autophagy, which is when parts of the cytoplasm are taken up into autophagosomes. In here, they are degraded and link up to the exogenous pathway (leading to MHCII).
What is MHC restriction?
MHC restriction is that a given T-cell is able to recognize a specific peptide only when bound to a specific self MHC molecule. For example, strain A animals only respond to Ag presented by strain A APCs but not by strain B APCs.
What causes the main mechanism of rejection of transplanted organs between genetically different individuals of the same species?
Allorecognition
What is allorecognition? How often does this occur?
Allorecognition is the recognition by some T-cells in the body of non-self MHC. 1-10% of all T-cells in an organism can react to non-self (allogeneic) MHC molecules (allo-MHC).
What genes are MHC molecules coded by?
MHC molecules are coded by human leukocyte antigen (HLA) genes.
Where are HLA genes found in humans?
HLA genes are found on chromosome 6.
True or False?:
There is only one allele of each MHC gene.
False
Many MHC genes have more than 100 different alleles.
What is polymorphism?
Polymorphism is when there are multiple variations (alleles) for a given gene that occupy the same locus.
What are haplotypes?
Haplotypes are the linked groups of allelic forms of MHC genes that are inherited from one’s parents (one from each parent).
In what manner are MHC alleles expressed? How is this beneficial?
MHC alleles are expressed codominantly, meaning that both maternal and paternal MHC genes are expressed in offspring cells. This gives the best chance for an organism to have some capability of presenting all the possible antigen peptides it encoutners.
Where are differences in MHC found? Why is this beneficial?
Difference are clustered at amino acid locations within the groove sites. This makes sense because if the areas outside the groove were changed too much, the new conformation might bind nothing.
True or False?:
A given MHC molecule can bind numberous different peptides and some peptides can bind to severeal different MHC molecules.
True
