A Weakened Immune Response to Synthetic Exo-Peptides Predicts a Potential Biosecurity Risk in the Retrieval of Exo-Microorganisms

SIMPLE SUMMARY: We tested the immune response of T cells of the mammalian immune system towards protein antigens that includes the unusual amino acids isovaline and α-aminoisobutyric. Those amino acids have been found in high abundance on carbonaceous meteorites but are extremely rare in proteomes of earth organisms. We hypothesised that proteins of non-terrestrial alien life forms might contain such amino acids and tested whether chemically synthesised “exopeptides” that contain these amino acids could be detected by the immune system. Our assays, based on the responses of CD8(+) T cells to these exopeptides, indicated that antigen cleavage, processing, and subsequent T cell activation still occurred, but were less efficient than the response to control peptides that lacked these amino acids. We therefore speculate that the encounter of putative exo-microorganisms of an unusual antigenic repertoire might pose an immunological risk for space missions aiming to retrieve potentially biotic samples from exoplanets and moons. ABSTRACT: The discovery of liquid water at several locations in the solar system raises the possibility that microbial life may have evolved outside Earth and as such could be accidently introduced into the Earth’s ecosystem. Unusual sugars or amino acids, like non-proteinogenic isovaline and α-aminoisobutyric acid that are vanishingly rare or absent from life forms on Earth, have been found in high abundance on non-terrestrial carbonaceous meteorites. It is therefore conceivable that exo-microorganisms might contain proteins that include these rare amino acids. We therefore asked whether the mammalian immune system would be able to recognize and induce appropriate immune responses to putative proteinaceous antigens that include these rare amino acids. To address this, we synthesised peptide antigens based on a backbone of ovalbumin and introduced isovaline and α-aminoisobutyric acid residues and demonstrated that these peptides can promote naïve OT-I cell activation and proliferation, but did so less efficiently than the canonical peptides. This is relevant to the biosecurity of missions that may retrieve samples from exoplanets and moons that have conditions that may be permissive for life, suggesting that accidental contamination and exposure to exo-microorganisms with such distinct proteomes might pose an immunological challenge.