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Duck-Kyun Yoo (Team DK)

Built with Claude: Life Sciences

Germinal-center (GC) selection is almost always modeled along a single axis — antigen affinity. But B cells are also selected on a second axis: tolerance — how polyreactive/self-reactive an antibody is. That axis has been hard to use because it was not measurable at repertoire scale. We make it measurable directly from structure. We fold paired antibody Fv *monomers* from sequence (Boltz-2, ESMFold-v1, Protenix) — deliberately avoiding antibody–antigen complex prediction, which is still unreliable — and read a physicochemical tolerance axis, surface-displayed CDR charge, off the fold. The score is folder-invariant, agrees with crystallographic geometry, and transfers without retraining to an autoimmune (type-1-diabetes) repertoire and to a tissue-resolved human GC repertoire, where the axis is significantly constrained in GC B cells. We report the result honestly, including the null (as a black-box predictor, folded structure does not beat a charge baseline out of distribution) and the one surviving charge-orthogonal signal. The output is a mechanistic, reproducible coordinate that single-axis accounts of GC selection have lacked. Results (attached again just in case): https://github.com/dk93js/gc_project, https://drive.google.com/drive/folders/19S4tkwlr4iTsHV2KyxBpoCAm1Cy821XO?usp=sharing

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