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June 3, 2026Proceedings of the National Academy of Sciences

HLA micropolymorphisms confine neoantigen conformational adaptability and guide T cell receptor selectivity

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Authors

JMJiaqi MaUniversity of Notre DameCACory M. AyresUniversity of Notre DameCBChad A. BrambleyUniversity of Notre Dame

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Implication

Research identifies how micropolymorphisms affect T cell receptor specificity, implying implications for immunotherapy.

Key Points

  • This research aims to understand how HLA micropolymorphisms influence TCR specificity and immune recognition.
  • Characterization of HLA-A*03:01 and HLA-A*03:02 polymorphisms.
  • Assessment of TCR binding with neoantigens derived from a PIK3CA mutation.
  • Analysis of the conformational ensembles of peptide/MHC complexes.
  • Micropolymorphisms in HLA-A*03:02 prevent TCR binding due to alterations in neoantigen conformational states.
  • TCRs unable to recognize the same neoantigen epitope across different HLA alleles despite similar presentation.
  • Discovery of a cross-groove interaction network that influences peptide/MHC adaptability.

Cite This Study

Ma et al. (2026) studied this question.

synapsesocial.com/papers/6a1fc7dcdee9eb8c0dce86dahttps://doi.org/10.1073/pnas.2602949123
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