Puneet Rawat, PhD

9/9 We also thank our generous funders:
@helmsleytrust.bsky.social , NIH, American Diabetes Association, @bt1dplay.bsky.social, EU Horizon 2020, iReceptorplus, Norwegian Cancer Society, Research Council of Norway, inno4vac, ERC Research, Marie Skłodowska-Curie Scientia fellows, nPOD.

@giulioisac.bsky.social, @mchernigovskaya.bsky.social, Sebastiaan Valkiers, Laura Jacobsen, @mike-haller.bsky.social , Desmond Schatz, Clive Wasserfall, Ryan Emerson, Andrew Gartland, Mark Atkinson, Günter Klambauer, Geir K Sandve etc.
Special thanks to @victorgreiff.bsky.social and Todd Brusko!! 🚀✨

7/9 We also extend our gratitude to the incredible team of collaborators who contributed to this giant effort.
Melanie Shapiro, Leeana Peters, Michael Widrich, Koshlan Mayer-Blackwell, Keshav Motwani, Ghadi al Hajj, Amanda Posgai, @milenapavlovic.bsky.social , @chakri.bsky.social

Identification of a type 1 diabetes-associated T cell receptor repertoire signature from the human peripheral blood Type 1 Diabetes (T1D) is a T-cell mediated disease with a strong immunogenetic HLA dependence. These HLA alleles influence T cell receptor (TCR) repertoire bidirectionally that shape thymic selection ...

6/9 📄 If you've read this far and are curious for more, dive into the full paper for details:
🧬 HLA-TCR associations
🤖 ML & deep learning analyses
🔍 TCR motif enrichment
And much more here: www.medrxiv.org/content/10.1...

5/9 Key takeaway: T1D-associated TCR motifs reflect HLA-driven genetic risk and show potential as biomarkers for disease monitoring and diagnostics. 🚀 Using state-of-the-art methods, this study deepens our understanding of autoimmune T cell responses in T1D. 🧬🔍

4/9 Public TCR clones weren’t shared across T1D individuals. Instead, we identified enriched/underrepresented motifs – distinct amino acid patterns in the CDR3β region. These motifs were validated in independent sorted cohorts of pLN and spleen, supporting their relevance. 🔗

3/9 Key findings:
🔹 HLA risk alleles restricts TCR diversity in T1D, revealing HLA-specific motifs.
🔹 ML/DL achieved an AUROC of 0.77 for identifying T1D status solely from TCR repertoires.
🔹 T1D-specific TCR motifs? Yes! But subsequence patterns not public clones. 🔗

2/9 We explored several key questions: How do HLA risk alleles shape the TCR repertoire? Can we identify a T1D-specific TCR signature in blood 🧪, with or without HLA info? Is this signature also enriched in pLN & spleen of T1D patients? Are there T1D-specific public TCR clones? 🔍🔗

Happy to share our new collaborative work! 🚨 We analyzed 2250 TCR repertoires to uncover how HLA risk alleles shape immune autoreactivity in T1D. T1D-specific HLA-motifs were also validated in pancreatic lymph nodes (pLN) & spleen. 🧬🧵 #T1D #Immunology #TCR 1/9