Combinatorial pairing of independently recombined T cell receptor (TCR) α- and β-chains is central to diversifying the TCR repertoire. Although sequence motifs in one chain correlate with epitope reco...

An expanded atlas of human cells maps the expression of nearly all human transcription factors across 701 cell-type/tissue combinations and uncovers the heterogeneous nature of senescence across tissu...

Mutations found in Colombian families raised hopes for treatments. Altered patient data and suspect images call their benefits into question

Epstein–Barr virus (EBV) colonizes secondary lymphoid tissues to establish persistent infection and is strongly associated with malignancy and auto...

Washington University in St. Louis is an inaugural member of Third Coast Foundry, a new initiative designed to strengthen the combined presence of Midwestern universities in the San Francisco Bay Area...

​On the morning of July 3, Tsinghua University held the Appointment Ceremony for Professor Omar M. Yaghi as Chair Professor of Tsinghua University at the Main Building.

Join us at the Keystone Symposia on Neuroinflammation in Health and Disease, June 2026, in Whistler, with field leaders!

Nature - GPR15-guided CD8+ T regulatory cells control intestinal inflammation

Darwinian evolution of immunoglobulin genes within germinal centers (GCs) underlies the progressive increase in antibody affinity following antigen ex…

What began as a small, hard-to-see mole on her ankle became a life-threatening battle with Stage 4 melanoma.

Birds use a variety of navigational strategies, including the geomagnetic field, especially when other cues are not available, such as under overcast or nocturnal conditions. Magnetite particles in th...

In this assay, Raphael Kopan argues that focused emphasis on disease and translation stifles innovation, and outline the reasons why, in my opinion, d…

The largest gift in Washington University in St. Louis history, from the Bursky Family Foundation, will advance the School of Public Health’s vision in a post-pandemic world.

T cell receptor (TCR) affinity enhancement can introduce off-target cross-reactivity with life-threatening consequences, as illustrated by the MAGE-A3-specific A3A TCR, which caused fatal cardiotoxicity through recognition of a Titin-derived peptide. Here, we reconstructed the crossreactivity landscape by reverse-engineering A3A toward its wild-type precursor, generating intermediate variants in which engineered CDR2α residues are systematically reverted to the wild-type sequence. Reverting just two engineered residues yields a receptor, v9, that retains MAGE-A3 cytotoxicity comparable to A3A while eliminating Titin and other acquired cross-reactivities. Structurally, these substitutions reduce CDR2α-MHC contacts and disrupt an intra-TCR CDR2α-CDR3β interaction, propagating conformational changes across CDR3 loops that reshape peptide engagement without altering docking geometry. These results demonstrate that mutations outside the peptide-contacting CDR3 loops can allosterically reconfigure antigen specificity and establish simple stepwise reverse engineering to wild-type as a strategy for correcting TCR cross-reactivity. ### Competing Interest Statement The authors have declared no competing interest. Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS), China, 2018-I2M-2-002 and 2024-I2M-2-001-1 Cancer Research UK (CRUK) DPhil in Cancer Science Award, C2195/A31310, CANCTA-2024/100004 Wellcome Trust, https://ror.org/029chgv08, 227585/Z/23/Z, 227388/Z/23/Z Cancer Research UK, DRCCIP-Nov23/100004 Engineering and Physical Sciences Research Council, https://ror.org/0439y7842, EP/S024093/1 Biotechnology and Biological Sciences Research Council, BB/T008784/1 Wellcome Trust Core Award, 203141/Z/16/Z Novo Nordisk Foundation Postdoctoral Fellowship, NNF23OC0082912 Gates Foundation, INV-055780 CSC-COI MD/PhD High-level Medical Innovative Talent Scholarship, 2024-I2M-2-001-1 ARISE Fellowship - Marie Skłodowska-Curie Actions, 945405

Some 10,109 doctoral-trained experts in science and related fields left their jobs last year as President Donald Trump dramatically shrank the

mRNA–lipid-nanoparticle vaccines do not require type 1 conventional dendritic (cDC1) cells or the WDFY4-dependent cross-presentation pathway for CD8+ T cell priming but, instead, engage both cDC1 and ...