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CD4 and CD8 co-receptors modulate functional avidity of CD1b-restricted T cells

Author

Listed:
  • Charlotte A. James

    (University of Washington)

  • Yuexin Xu

    (Clinical Research Division, Fred Hutchinson Cancer Research Center)

  • Melissa S. Aguilar

    (University of Washington)

  • Lichen Jing

    (University of Washington)

  • Erik D. Layton

    (University of Washington)

  • Martine Gilleron

    (Université de Toulouse, CNRS, UPS)

  • Adriaan J. Minnaard

    (University of Groningen)

  • Thomas J. Scriba

    (University of Cape Town)

  • Cheryl L. Day

    (Emory University)

  • Edus H. Warren

    (University of Washington
    Clinical Research Division, Fred Hutchinson Cancer Research Center
    University of Washington
    Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center)

  • David M. Koelle

    (Clinical Research Division, Fred Hutchinson Cancer Research Center
    University of Washington
    University of Washington
    University of Washington)

  • Chetan Seshadri

    (University of Washington
    Tuberculosis Research and Training Center)

Abstract

T cells recognize mycobacterial glycolipid (mycolipid) antigens presented by CD1b molecules, but the role of CD4 and CD8 co-receptors in mycolipid recognition is unknown. Here we show CD1b-mycolipid tetramers reveal a hierarchy in which circulating T cells expressing CD4 or CD8 co-receptor stain with a higher tetramer mean fluorescence intensity than CD4-CD8- T cells. CD4+ primary T cells transduced with mycolipid-specific T cell receptors bind CD1b-mycolipid tetramer with a higher fluorescence intensity than CD8+ primary T cells. The presence of either CD4 or CD8 also decreases the threshold for interferon-γ secretion. Co-receptor expression increases surface expression of CD3ε, suggesting a mechanism for increased tetramer binding and activation. Targeted transcriptional profiling of mycolipid-specific T cells from individuals with active tuberculosis reveals canonical markers associated with cytotoxicity among CD8+ compared to CD4+ T cells. Thus, expression of co-receptors modulates T cell receptor avidity for mycobacterial lipids, leading to in vivo functional diversity during tuberculosis disease.

Suggested Citation

  • Charlotte A. James & Yuexin Xu & Melissa S. Aguilar & Lichen Jing & Erik D. Layton & Martine Gilleron & Adriaan J. Minnaard & Thomas J. Scriba & Cheryl L. Day & Edus H. Warren & David M. Koelle & Chet, 2022. "CD4 and CD8 co-receptors modulate functional avidity of CD1b-restricted T cells," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27764-w
    DOI: 10.1038/s41467-021-27764-w
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    References listed on IDEAS

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    1. Dietmar Zehn & Sarah Y. Lee & Michael J. Bevan, 2009. "Complete but curtailed T-cell response to very low-affinity antigen," Nature, Nature, vol. 458(7235), pages 211-214, March.
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