ATLAS: A database linking binding affinities with structures for wild-type and mutant TCR-pMHC complexes

Area of Science:

• Immunology
• Structural Biology
• Bioinformatics

Background:

• T cell receptors (TCRs) mediate adaptive immunity by recognizing peptide-major histocompatibility complex (pMHC) antigens.
• Understanding TCR-pMHC interactions is crucial for developing immunotherapies and vaccines.
• Existing databases lack comprehensive integration of binding affinities and structural data for TCR-pMHC complexes.

Purpose of the Study:

• To establish the ATLAS database, a manually curated repository of TCR binding affinities and associated 3D structures.
• To link experimentally measured binding affinities with corresponding TCR-pMHC complex structures.
• To facilitate the development of protein design algorithms targeting TCR-pMHC interactions.

Main Methods:

• Manual curation of binding affinities for wild-type and mutant TCRs and their pMHC antigens.
• Integration of experimentally measured binding affinities with 3D structural data of TCR-pMHC complexes.
• Generation of structural models for mutant TCRs using the Rosetta program.

Main Results:

• The ATLAS database provides a searchable collection of TCR-pMHC binding affinities and structures.
• Structural models for mutant TCRs were generated and made available.
• A correlation of 0.63 was observed between experimentally measured and predicted changes in binding energies.

Conclusions:

• The ATLAS database serves as a valuable resource for studying TCR-pMHC interactions.
• The integrated data and structural models can accelerate the design of novel protein-based therapeutics.
• This resource supports the advancement of computational approaches in protein engineering and drug discovery.