1/ In two back-to-back papers, we present our de novo TRACeR platform for targeting MHC-I and MHC-II antigens TRACeR for MHC-I: go.nature.com/4gcLzn5 TRACeR for MHC-II: go.nature.com/4gj5OQk - ThreadSky

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possuhuanglab.bsky.social • 72 days ago

1/ In two back-to-back papers, we present our de novo TRACeR platform for targeting MHC-I and MHC-II antigens

TRACeR for MHC-I: http://go.nature.com/4gcLzn5
TRACeR for MHC-II: http://go.nature.com/4gj5OQk

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possuhuanglab.bsky.social•72 days ago

2/ MHC antigens are central to the immune system and can be leveraged for disease-specific targeting. These peptides are derived from intra-cellular proteins and ingested foreign antigens for presentation by class-I and class-II MHCs, respectively.

possuhuanglab.bsky.social•72 days ago

3/ Peptides in MHC-II are in an extended conformation. TRACeR-II uses a surface loop to reach into MHC-II’s peptide binding groove to recognize the peptide. We use a single loop to convey specificity to the peptide in the binding groove.

possuhuanglab.bsky.social•72 days ago

4/ But MHC-I peptides have bulged conformations. For TRACeR-I, we use a set of spatially-defined amino acid residues to “box-in” on the peptide and achieve recognition.

possuhuanglab.bsky.social•72 days ago

5/ The mechanism of TRACeR-1 can achieve discrimination of single point mutants to peptides.

possuhuanglab.bsky.social•72 days ago

6/ We show proof-of-concept targeted killing of tumor cells using TRACeR-I.

possuhuanglab.bsky.social•72 days ago

7/ Our platform offers a convenient strategy for creating MHC binders: from a master library, peptide-specific MHC binders can be isolated simply by a few rounds of yeast surface display enrichment.

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