Here what CDC writes about COVID-19 mRNA: " COVID-19 mRNA vaccines are given in the upper arm muscle. Once the instructions (mRNA) are inside the muscle cells, the cells use them to make the protein piece. After the protein piece is made, the cell breaks down the instructions and gets rid of them.
Next, the cell displays the protein piece on its surface. Our immune systems recognize that the protein doesn’t belong there and begin building an immune response and making antibodies, like what happens in natural infection against COVID-19."
1) From classic immunology we know that muscle cells are not the antigen-presenting cells.
2) We know that intracellular proteins are being presented in class I MHC to CD8 T cells, which in this case, have not been "trained" in thymus for this antigen.
So how are we sure, that these mRNA will not trigger myolytic /autoimmune response towards the muscular MHC class I/COVID-19 complex?
Priming T cell responses (both naive or pre-existing memory responses) requires additional co-stimulation in addition to the initial TCR/pMHC contact. This occurrs in secondary lymphoid tissue such as lymph nodes or spleen. So what needs to happen is that the vaccinating antigen needs to arrive in draining lymph nodes near the site of injection where professional antigen presenting cells can present the epitopes on both class I and II molecules and also provide the necessary co-stimulation.
If the vaccinating antigen enters muscle tissue (non-professional antigen presenting cells), then any naive or memory T cells that start recognizing it will, rather than attacking that tissue, will actually become inactive (anergic) because they have not been properly primed.
Well, that is why we give the vaccines, to properly prime the CD4 and induce a germinal center reaction leading to maturation of memory cells with further synthesis of neutralizing antibodies.
While all other vaccines are proteins per nature/or inactivated pathogen, this one is mRNA, and in the place of alteration (injection site) we will have muscle cells, who present the viral epitopes attached to MHC-I, we will have dendritic cells too in the locus, which will catch up mRNA and present epitopes with MHCI, we may have dendritic cells which will catch the synthesized protein and present with MHCII, or both.
As the inflammatory locus is in the injection site, nearby we will have CD8 cells, reactive to MHC-I+viral epitopes, which in the same nature may get activated via APC licensing or even bystander activation.
This also depend of the amount and the nature of cells initially transfected after the Covid RNA vaccination; have we experimental informations about that ?
I do not know, but for that one should take the muscle cells/fibroblast before- and after- the administration of the vaccine. Take lymphocytes from the same animal, separate B and T cells before- and after- the administration of the vaccine. And then cross-culture each muscle/fibroblast with each set of lymphocytes with- and without IL-2. Check the result by cytotoxicity. After that, probably do some tetrameric assay. In Russia, they started to administer Sputnik-V. I'd longitudinally measure CPK levels for a set of people who received that vaccine.
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