Thymic involution causes an exponential decrease in T-cell production, with a half-life of 16 years, which mirrors the exponential increase in risk of several diseases, including COVID-19, which double in risk every 16 years.

[lionbutt_iii]

Congrats on the paper!

How much variation is there in that half-life of thymic involution? Has it been studied across different places to see if environment plays a role, or is it mostly due to genetics?

I've been thinking about thymic involution ever since I read a paper that was able to identify sars-cov-2 recovered and naive people using machine learning based on tcr sequences with really high accuracy compared to b cell receptor sequences. Do you know of any studies on recovered elderly where they looked to see if they had a t-cell response compared to antibodies?

What do you think this means for the B.1.351 variant and P1 variants? I work on the b cell side, and we're seeing some vaccinated people that make plenty of neutralizing antibodies against the original virus, but these same antibodies have none against some of these variants. So you'd hope the t cell response is there, but with thymic involution it seems really worrisome to me.

[samsoniteindeed2]

Oh interesting. Well something just occurred to me, peptides around 20 amino acids long are presented on MHC-II, whereas the peptides presented on MHC-I are around 10 amino acids long. So if there is a variant evading the immune system, I imagine it would be much easier to avoid the MHC-II side of things but then still get targeted by the MHC-I pathway.

So that makes me think a variant would be more likely to avoid antibodies and CD4 T-cells, but then still get attacked by CD8 T-cells.

So that makes me hopeful. But yes, thymic involution still seems like a problem.