Conformational bias in SARS-CoV-2 Spike CD4+ T-cell epitope dominance - Summary - MDSpire

Conformational Influence on Dominance of CD4+ T-cell Epitopes in SARS-CoV-2 Spike Protein

  • By

  • Samuel J. Landry

  • N. Kalaya Steede

  • Yali Tiomkin

  • Haley Smith

  • Ramgopal R. Mettu

  • Loren Gragert

  • Judith H. Aberle

  • Kevin J. Zwezdaryk

  • Crystal Zheng

  • Jay K. Kolls

  • Bronwyn M. Gunn

  • Amelie E. Murrell

  • Ivy V. Trinh

  • John S. Schieffelin

  • James E. Robinson

  • Elizabeth B. Norton

  • July 20, 2026

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Objective:

To analyze how the conformation of the SARS-CoV-2 spike protein influences the dominance of CD4+ T-cell epitopes.

Approach:
  • Modeling and Analysis: Limited proteolysis of soluble spike trimer was performed, and CD4+ T-cell epitope dominance was analyzed using IL-2 Elispots with two nine-peptide pools from stable and unstable regions of the spike.
Key Findings:
  • Protease-sensitive sites coincided with domain boundaries and conformationally unstable regions, confirming that structure limits proteolysis.
  • The ratio of CD4+ T-cell responses to stable versus unstable peptide pools varied between cohorts exposed through infection or vaccination.
Interpretation:

Limitations:
  • The study primarily focuses on limited human cohorts, which may not represent broader populations.
  • The influence of other factors on T-cell responses was not fully explored.
Conclusion:

Original Source(s)

Conformational bias in SARS-CoV-2 Spike CD4+ T-cell epitope dominance

  • by Samuel J. Landry, N. Kalaya Steede, Yali Tiomkin, Haley Smith, Ramgopal R. Mettu, Loren Gragert, Judith H. Aberle, Kevin J. Zwezdaryk, Crystal Zheng, Jay K. Kolls, Bronwyn M. Gunn, Amelie E. Murrell, Ivy V. Trinh, John S. Schieffelin, James E. Robinson, Elizabeth B. Norton

  • July 20, 2026

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