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This article reported that scientists have succeeded in adding two new bases to the quartet of A, C, G and T, resulting in non-canonical amino acid. Additionally, the bacteria in which this was done were able to produce new proteins using the newly added bases. The article quotes the scientists as saying that the extra amino acids “might become building blocks for new drugs and novel materials”.

My question is that if new proteins are made from amino acids that don’t naturally occur, won’t the body reject them?

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  • $\begingroup$ The article you cite is a review of a paper in Nature, which nowhere mentions the "new protein drugs" the journalist quotes. It is therefore difficult to comment on whether or not immune rejection will be a problem. I suggest you do some more research to find out more about these claims. The scientist will obviously be aware of the problem of immune rejection, but remember, most diabetics can tolerate pig insulin, which differs from human insulin. $\endgroup$ – David Jan 9 at 20:30
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The body's mechanism for detecting foreign object has a built-in failsafe that minimizes the likelihood of misinterpreting a self-derived antigen as foreign.

Immunologic tolerance (unresponsiveness) normally prevents reactions against self-antigens; if immunologic tolerance is broken, autoimmune reactions may occur. Much of the development of tolerance occurs in the thymus by the elimination (clonal deletion) or inactivation (clonal anergy) of self-reactive clones of T cells. Other mechanisms of tolerance occur extrathymically and include activation of antigen-specific T suppressor cells and clonal deletion, which results in the elimination of self-reactive B cells or T cells, and clonal anergy.

https://www.ncbi.nlm.nih.gov/books/NBK7795/

Basically, before a T cell starts looking for potential antigens, it generally first spends some time in the thymus being tested against antigens which are native to the body. If it responds to such an antigen, the T cell will either be destroyed or deactivated.

Having unnatural amino acids as part of this process is unlikely to change its efficacy. T cells which would target peptides with these unnatural amino acids will still be checked against the body's cells before being sent out to do their work; the mechanism would work the same way. I suspect that the rate of autoimmune diseases would be unchanged compared to normal organisms.

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  • $\begingroup$ What do you mean by "before a T cell starts looking for potential antigens" and "T cells … will be checked against the body's cells"? The quotation states that tolerance occurs by elimination of cells that would be self-reactive. Your gloss seems at variance with this. $\endgroup$ – David Jan 8 at 11:37
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    $\begingroup$ @David tolerance occurs both during and after development and the quote clearly indicates that by saying "Much of ... Other mechanisms ... ". The "gloss" seems perfectly reasonable for a short summary of a very complex topic. $\endgroup$ – iayork Jan 8 at 18:50
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    $\begingroup$ @David The quote states that tolerance occurs by elimination or inactivation of self-reactive cells. I simplified that to "won't be used", since many of them are inactivated instead of destroyed. $\endgroup$ – Astrolamb Jan 9 at 2:27
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    $\begingroup$ @David I'm not sure I understand your criticism here. The point of Astrolamb's answer is that the mechanism for avoiding autoimmune reactions doesn't depend on the identity of any particular amino acids, it merely depends on the presence of antigen during T-cell development. A novel protein with standard amino acids and a novel protein with an extra non-standard amino acid will be treated the same. $\endgroup$ – Bryan Krause Jan 9 at 20:46
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    $\begingroup$ @David The authors aren't anywhere near that point, they are just working on inserting this into a bacterium. The news article suggests someday these could be useful, OP was wondering if immune responses would be an issue, Astrolamb says a novel amino acid won't matter because detecting individual amino acids is not how the immune system recognizes 'self.' If your argument is that "looking" is too anthropomorphic, I think that's far too nitpicky, the sentiment in the answer is clear. $\endgroup$ – Bryan Krause Jan 9 at 21:56

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