Gonzalez, A. P. | Search bioRxiv

bioRxiv2026

Specific targeting of MR1-antigen complexes using nanobodies

T cell receptor mimic (TCRm) antibodies and nanobodies that specifically bind peptide-HLA complexes have great therapeutic potential, as they can target polymorphic HLA on tumour cells furnishing peptides derived from tumour-associated antigens. MR1 is an MHC class-I-like molecule that exhibits limited polymorphism that binds and presents conserved metabolites, such as 5-OP-RU, derived from microbial riboflavin biosynthesis. Whether antibodies targeting such MR1-5-OP-RU complexes can be generated remains unclear. Using yeast display technology and in vitro affinity maturation, a nanobody with high affinity and fine specificity toward MR1-5-OP-RU complex was generated. These nanobodies bind both mouse and human MR1-5-OP-RU and inhibited MAIT cell responses to 5-OP-RU in vitro and in vivo demonstrating therapeutic potential. Moreover, we provide a molecular basis underpinning the fine specificity of these nanobodies, solving the crystal structures of MR1 in complex with either 5-OP-RU or Ac-6-FP. Here, the nanobody co-bound MR1 and 5-OP-RU, akin to a TCRm antibody. Moreover, we engineer bispecific antibodies targeting both MR1-5-OP-RU and CD3, that drive broad T cell killing of bacterially-infected cells as well as tumour cells treated with 5-OP-RU, thereby providing proof-of-principle for targeting the MR1 molecule with with TCRm-based nanobodies. One Sentence SummaryWe report the development of a nanobody targeting MR1-5-OP-RU complex and demonstrate its utility to modulate MAIT cells responses, and as a bispecific engager.

immunology↗

bioRxiv2025

Beyond magnetosomes: ubiquitous and diverse intracellular inclusions expand the role of magnetotactic bacteria in biogeochemical cycling

Magnetotactic bacteria (MTB) are capable of accumulating and storing intercellular pools containing phosphorus, sulfur, nitrogen and carbon. Yet, the metabolic pathways connected with their intracellular storage of polyphosphate, elemental sulfur, nitrate, and calcium carbonate, and the environmental influence on MTB inclusions and their quantitative contribution to sedimentary chemical budgets remain underexplored. Using a combination of chemical characterization, ultrastructural and compositional analyses, and phylogenetic and genomic insights into microbial assemblages, we investigated the influence of geochemical parameters on the diversity, ecophysiology, and distribution of MTB in freshwater and brackish sediments. Special focus is given to intracellular inclusions and their metabolic pathways to uncover functional traits and ecological roles in elemental cycling. Of the 118 examined MTB cells, polyphosphate granules (75%) and nitrate-containing vacuoles (67%) were the most common inclusions followed by sulfur globules (25%) and calcium carbonate granules (8%). The intracellular phosphorus, nitrogen, and sulfur stored in MTB cells were conservatively estimated to account for 0.60%, 0.91%, and 0.23% of the total sedimentary P, N, and S in the investigated freshwater sediments, respectively. The ubiquitous nature and important ecological role of MTB can be explained by their ability to sequester chemical elements into intracellular inclusions, giving them a metabolic advantage in dynamic chemically stratified environments. The extraordinary phylogenetic diversity of MTB, coupled with their capability to hyperaccumulate and store a wide range of elements and compounds, represents a significant resource for biotechnology innovation.

microbiology↗