TCRmodel

TCRmodel models T cell receptors (TCRs) by generating high-resolution three-dimensional structural models from repertoire-level and deep sequencing TCR sequence data to enable analysis of antigen recognition and cross-reactivity.

Key Features:

• Rosetta-based algorithm: Implements a novel modeling algorithm within the Rosetta program to construct TCR structures from sequence inputs.
• Sequence-to-structure modeling: Produces high-resolution 3D structural models of TCR variable regions from repertoire-level and deep sequencing-derived sequences.
• High-throughput model generation: Generates models rapidly to support large-scale immune repertoire analysis.
• Benchmarking and accuracy: Validated against nonredundant recently released TCR crystal structures and shown to compare favorably with other available modeling methods.

Scientific Applications:

• Vaccine design: Structural models of TCRs inform how TCRs recognize antigens to guide vaccine epitope selection and design.
• Autoimmunity studies: Structural characterization of TCRs aids identification of autoreactive specificities and potential therapeutic targets in autoimmune disease.
• Cancer immunotherapy: Modeling TCR recognition of tumor-associated antigens supports development and redesign of TCRs for personalized cancer therapies.

Methodology:

A Rosetta-implemented algorithm constructs high-resolution TCR models from sequence data and the approach was benchmarked against nonredundant recently released TCR crystal structures.