TfR1
Transferrin receptor 1 (CD71)
Design a conditional TfR1 binder
TfR1 carries iron-loaded transferrin into cells and recycles to the surface once the iron is released in the acidifying endosome. Every dividing cell uses it, the blood-brain barrier expresses it highly, and antibodies against it are the most advanced way to ferry drugs into the brain. It is a disulfide-linked homodimer with three domains per subunit. This challenge asks for the same three things as the TNF-α challenge: bind human TfR1, bind the mouse receptor as well, and hold human TfR1 at pH 7.4 but let go at pH 6.0.
Human TfR1 ectodomain homodimer · PDB 11QC
Target information
Design against the soluble ectodomain, supplied as a homodimer. We recommend targeting a functional epitope such as the apical domain, the tip of each subunit that viruses and brain-shuttle antibodies bind, which leaves the transferrin site free.
Human TfR1
Ectodomain homodimer- UniProt reference
- P02786-1 ↗
- Target residues · UniProt
- 121–760 / 640 aa
- Assay construct
- Ectodomain 121–760 · tag-free
- Recommended epitope
- Apical domain
- Structure reference
- 11QC · Chains A–B ↗
- Apical-domain complex
- 11RN · Chain A with VP1u ↗
Amino acid sequence
RLYWDDLKRKLSEKLDSTDFTGTIKLLNENSYVPREAGSQKDENLALYVENQFREFKLSKVWRDQHFVKIQVKDSAQNSVIIVDKNGRLVYLVENPGGYVAYSKAATVTGKLVHANFGTKKDFEDLYTPVNGSIVIVRAGKITFAEKVANAESLNAIGVLIYMDQTKFPIVNAELSFFGHAHLGTGDPYTPGFPSFNHTQFPPSRSSGLPNIPVQTISRAAAEKLFGNMEGDCPSDWKTDSTCRMVTSESKNVKLTVSNVLKEIKILNIFGVIKGFVEPDHYVVVGAQRDAWGPGAAKSGVGTALLLKLAQMFSDMVLKDGFQPSRSIIFASWSAGDFGSVGATEWLEGYLSSLHLKAFTYINLDKAVLGTSNFKVSASPLLYTLIEKTMQNVKHPVTGQFLYQDSNWASKVEKLTLDNAAFPFLAYSGIPAVSFCFCEDTDYPYLGTTMDTYKELIERIPELNKVARAAAEVAGQFVIKLTHDVELNLDYERYNSQLLSFVRDLNQYRADIKEMGLSLQWLYSARGDFFRATSRLTTDFGNAEKTDRFVMKKLNDRVMRVEYHFLSPYVSPKESPFRHVFWGSGSHTLPALLENLKLRKQNNGAFNETLFRNQLALATWTIQGAANALSGDVWDIDNEFBoth constructs are the ectodomain from the start of the protease-like domain to the C-terminus (human 121–760, mouse 123–763), with no tag left after cleavage (a Gly-Pro scar before the first residue is not shown). The receptor is a homodimer in solution, so each target presents two copies of the epitope.
Three objectives
This challenge consists of 3 main objectives, and each will be accounted for when selecting the best designs.
01
Binding affinity
Design a binder against human TfR1. We recommend targeting a functional epitope such as the apical domain, which New World arenaviruses and parvovirus B19 use to enter cells and which brain-shuttle antibodies bind, so that transferrin can still dock and the receptor keeps recycling.
We'll measure its binding affinity using the soluble ectodomain of human TfR1, supplied as a homodimer.
02
Mouse cross-reactivity
In the next objective, you should design a binder that recognises both human and mouse TfR1. On top of the validation from Objective 1, we will test binding against mouse TfR1 at pH 7.4.
TfR1 binders are notoriously species-specific, and antibodies for brain delivery are usually made twice, once for mouse studies and once for humans. The two ectodomains are 78% identical, and the apical patch differs at six of nine positions.
How designs are ranked
Every tested design is measured in the same four conditions: human TfR1 at pH 7.4 and at pH 6.0, and mouse TfR1 at pH 7.4, with the design immobilised and the target in solution. A design counts as binding in a condition when its sensorgram gives a fittable curve and a KD, or, where the curve cannot be fitted, when the association shift clears 300% over the negative control. Otherwise we call it no detectable binding.
- 1
pH-selective binding
A measurable KD against human TfR1 at pH 7.4 and no detectable binding at pH 6.0. Designs that bind at both pH values rank after these, by the ratio of their KD at pH 6.0 to their KD at pH 7.4. Designs that rely on a conformational change or a designed pH mechanism are not penalised when we select designs for testing; the measurement decides.
- 2
Mouse cross-reactivity
Binds mouse TfR1 as well as human at pH 7.4, ranked by how close the mouse-to-human KD ratio is to 1, among designs whose human KD is below 1 µM.
- 3
Affinity
Lowest KD against human TfR1 at pH 7.4. Binding at a functional epitope counts in its favour: name the epitope you target and link your evidence, or we read it from a predicted complex. The recommended epitope is a hint, not a rule: a design that binds elsewhere is measured and ranked all the same.
The winner has to clear all three steps, with ties settled in this order, and each step also awards an honourable mention to the best design that did not win.
Which designs are tested is a separate step from who wins. Track 1 teams get their ranked designs tested; for Tracks 2 and 3, Claude selects from all submissions with a prompt we publish in full.
Timeline
Oct 19 – Nov 1, 2026
- 1nowSubmit designs
Submissions open
Design, review, and submit. Submissions close Sunday, November 1 at 23:59 Anywhere on Earth (AoE).
- 2
Submissions closed
The window is closed. No further designs are accepted for this challenge.
- 3
Selection in progress
Anthropic and Adaptyv select designs for synthesis using a Claude-based workflow, published after the competition.
- 4
Wet-lab validation in progress
Selected designs go to Adaptyv's automated lab for experimental validation.
Submission requirements
- Length
- 10–250 amino acids
- Format
- Single chain protein, nanobody, scFv, or Fab
- Designs per participant
- Up to 40 for Track 1, up to 20 for Tracks 2 and 3
- Design
- De novo designs only