Tregitopes by Another Name?

by | Mar 26, 2024 | Thinking Out Loud -Blog

OK, sometimes, I am late to the party. Maybe … allowing ideas, like parties, to mature, means getting there at exactly the right time. That just happened with this article and I’d like to share it with you. It’s about Tregitopes, even though the authors … beg to differ. And (ICYMI) what are Tregitopes? They are highly conserved sequences in IgG found right outside CDR regions and in the Fc domains…of monoclonal antibodies. (e.g. epitope ‘beret’ on the cute guy in this picture). We discovered them in 2008.
 
Currently, we hypothesize that they modulate the evolution of high affinity antibodies (long story short, more later). This article from none other than (shocked emoji) Alex Sette and Alessandra Franco shows that … wait for it …  IgG Epitopes (a.k.a. Tregitopes) Processed and Presented by IgG+ B Cells Induce Suppression by Human Thymic-Derived Regulatory T Cells. According to A & A, these peptides don’t overlap with Tregitopes … or do they? (see image). Voilà! … we’re glad to report this additional validation of Tregitopes 167 and 289 (below) despite … not calling them by their name. And yes, even more Tregitopes are found in IgG FAb domains. For more info, watch for the new ISPRI paper in mAbs!
 
OK Annie, so what does it all mean? It means Tregs that are activated by Tregitopes directly suppress antibody (read ADA) formation by reducing B cell activity. More Tregitopes, lower ADA! 
 
 

Meet ISPRI 2.0

Say hello to ISPRI 2.0! – The ISPRI Toolkit is bigger and more beautiful, thanks to Matt Ardito and his team. ICYMI – ISPRI is the integrated, online, secure access version of our state-of the art tools for in silico immunogenicity screening and protein engineering. We recently embarked on a listening tour – getting your suggestions – and now – check out the results ! 

Immunogenicity Scales – In Multiple Flavors!
Want to compare your novel therapeutic sequences to relevant sequences of known immunogenicity? We have four new benchmark groups on the Protein Immunogenicity Scales. Choose from Pathogens, Autologous Proteins, Scaffold Proteins and Protein Therapeutics. Are there other benchmarks that you would like to see added? Let us know!

And now the Antibody Analysis silo has new scales too! Want to see the combined Tregitope-adjusted EpiMatrix score for submitted VH/VL sequences and the predicted ADA? Just toggle at the top:

 
 

And … Epitope Maps!
See an example Epitope Map below for Avastin’s variable heavy domain. Don’t you love it? This is my favorite new feature. Validated Tregitopes are highlighted in green and blue frames show potential T effector epitopes.

IYKYK – JanusMatrix Quadrant Plots!

The quadrant plot allows you to consider both the EpiMatrix score (HLA binding potential) and the JanusMatrix score (humanness) on the same visua

 

 

 

It’s MaGIC!

Stay tuned for the MaGIC Report – a Machine-Generated Immunogenicity Content snapshot that puts all of your data on one single print out!

Want access to ISPRI? Say hello to Riley Nolan, our ISPRI Client Liaison.

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Local luminaries from the Broad Institute at MIT, Brown University, BU Medical Center, University of Rhode Island, and the region who are working at the AI/HI interface will be speaking. The current speaker list and agenda, is now available. I won’t be late to this party, and I look forward to seeing you!

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