Tumor antigens Flashcards
What MHC class presents tumor peptides
MHC class 1
Missense mutations
Swap one nucleotide for another, changing the amino acids sequence. small change but can have large impact.
can impact ATP binding, phosphorylation residues, or key folding amino acids.
What are INDELS
Insertion mutations- insert a nucleotide into the DNA chain, likely induces frameshift in the amino acids.
Deletion mutations- remove nucleotide from the DNA strand and can change reading frame.
Nonsense mutations
premature stop codons, missense, indels or other types can cause them.
Silent mutations
Not all tRNAs are expressed at the same frequency in humans and this leads to codon bias. silent mutations can impact expression as there is less tRNA available in order to continue translation.
Tumor-specific antigen (TSA) or Neoantigen
Commonly a result of mutations.
allows for amino acid/peptide sequences that are not found elsewhere in the body.
example is P53 which is master regulator of cell death.
Loss of P53
This causes cells to lose the ability to start apoptosis and this can increase the likelihood of tumor formation.
TSAs as immune targets.
highly desirable as immune targets as they are specific for the tumors.
Immuno-privileged tissues
are invisible to the immune cells like the testes and ovaries not expressed on MHC
commonly called cancer/testis antigen (C/TA)
CTAs
can be beneficial for tumors as they may provide growth factors, angiogenic factors and other promoters for tumor survival and growth.
one to know is MAGE+ NY-ESO-1
Do tumors only use mutated proteins?
No they do use mutated proteins and change their expression. If there is no specific antigen expression of a Tumor that is still an association called a Tumor associated antigen.
Tumor associated antigens (TAA)
Not ideal targets as the protein is expressed normally on some or all cells.
these are negatively selected for as this is catagorized as self.
Strong upregulation of a protein cane sometimes flood MHC1 w/ peptides of that protein, which can activate a T-cell w/ a weak affinity for that MHC and peptide combo
can cause immune response against TAAs which will be weaker and risker as this can cause autoimmunity.
TAAs are more common than TSAs
TAA type in one cell
Not specific to the tumor but is specific to a very limited cell type
can lose these cells w/o issue.
if the antigen was shared with heart of brain tissue you would activate T-cells against the tumor but also cause death of essential organs
however melanomas derived from melanocytes can be targeted specifically.
Tumor antigens are always linear
false there ate non-linear peptides that generate T-Cell specific responses
example is melanocytes expressing a protein called gp100.
Leads to TSA because peptide sequence is not found elsewhere in the body
