Discussion in 'Other Health News and Research' started by AndyPR, Oct 23, 2016.
Brilliant, I do love science!
The article in Science is unfortunately behind a paywall, so I can't read it all (probably beyond me anyway), but the abstract is interesting:
'New players in the repertoire
Antigen-presenting cells, such as macrophages and dendritic cells, activate immunological T cells by presenting them with antigens bound by major histocompatibility complexes (MHCs). The proteasome typically processes these antigens, which include peptides derived from both self and microbial origins. Liepe et al. now report that, surprisingly, a large fraction of peptides bound to class I MHC on multiple human cell types are spliced together by the proteasome from two different proteins. Such merged peptides might turn out to be useful in vaccine or cancer immunotherapy development.
The proteasome generates the epitopes presented on human leukocyte antigen (HLA) class I molecules that elicit CD8+ T cell responses. Reports of proteasome-generated spliced epitopes exist, but they have been regarded as rare events. Here, however, we show that the proteasome-generated spliced peptide pool accounts for one-third of the entire HLA class I immunopeptidome in terms of diversity and one-fourth in terms of abundance. This pool also represents a unique set of antigens, possessing particular and distinguishing features.
We validated this observation using a range of complementary experimental and bioinformatics approaches, as well as multiple cell types. The widespread appearance and abundance of proteasome-catalyzed peptide splicing events has implications for immunobiology and autoimmunity theories and may provide a previously untapped source of epitopes for use in vaccines and cancer immunotherapy.'
I love the way I keep coming across new '-omes'. I've heard of the genome, epigenome, proteome, matabolome, and microbiome, and the '-omics' that go with them.
Now here we have the proteasome and the immunopeptidome. Makes me wish I were decades younger and just getting going on my science degree... Sigh!
As the article states, spliced epitopes are not a new discovery. What is new is recognition of how common they are.
These markers complicate two important medical diagnostic problems: genetic analysis, and detection of autoantibodies. They also complicate treatments based on epitopes.
I have previously commented that in all cases where adoptive immunotherapy destroys pathological cells, and only those cells, researchers have carefully selected several epitopes to identify target cells. This is something active immune cells can be selected to do, but is not possible with monoclonal antibodies used in many medical interventions for serious diseases.
This kind of science revelation always gives me that 'MUPS" feeling of: there is always a physical explanation we just have as yet to unlock a more complete understanding of the mysteries of the human body and how it functions.
And if medical practitioners want to suggest somatic illness they are going to have to cough up some evidence.
This new discovery seems to have import for understanding how autoimmunity might arise:
Perhaps @Jonathan Edwards might find this of interest.
Hmm, it seems like a very mundane finding being hyped to me. This is, as far as I can see, about the peptides that get put into class I molecules for antigen presentation. We know there is a huge amount of randomness in that process. This may suggest even more randomness - possibly as a way of catching viral antigens that might otherwise escape by not providing peptides that on their own would look 'foreign' in a class I groove. I cannot personally see what it would have to do with autoimmunity. The randomness underlying autoimmunity occurs somewhere quite different - in the immunoglobulin genes.
Thank you @Jonathan Edwards. We need you here to bring us back to earth with a bump when we get overexcited by every new scientific development that might or might not be relevant to us. I always look out for your comments and value them.
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