CD1b-mycolic acid tetramers demonstrate T-cell fine specificity for mycobacterial lipid tails

Ildiko Van Rhijn, Sarah K. Iwany, Peter Fodran, Tan-Yun Cheng, Laurent Gapin, Adriaan J. Minnaard, D Branch Moody

    Research output: Contribution to journalArticleAcademicpeer-review

    Abstract

    Mycobacterium tuberculosis synthesizes a thick cell wall comprised of mycolic acids (MA), which are foreign antigens for human T cells. T-cell clones from multiple donors were used to determine the fine specificity of MA recognition by human αβ T cells. Most CD1-presented lipid antigens contain large hydrophilic head groups comprised of carbohydrates or peptides that dominate patterns of T-cell specificity. MA diverges from the consensus antigen motif in that it lacks a head group. Using multiple forms of natural and synthetic MA and MA-specific T-cells with different T-cell receptors, we found that, unlike antigens with larger head groups, lipid length strongly controlled T-cell responses to MA. In addition, the three forms of MA that naturally occur in M. tuberculosis that differ in modifications on the lipid tail, differ in their potency for activating MA-specific T-cell clones. Thus, naturally occurring MA forms should be considered as separate, partly cross-reactive antigens. Two of the three forms of MA could be loaded onto human CD1b proteins, creating working CD1b-MA tetramers. The creation of CD1b-MA tetramers represents a new tool for future studies that track the effector functions and kinetics of MA-specific T-cells ex vivo.
    Original languageEnglish
    Pages (from-to)1525-1534
    Number of pages10
    JournalEuropean Journal of Immunology
    Volume47
    Issue number9
    DOIs
    Publication statusPublished - 1 Sept 2017

    Keywords

    • Antigen specificity
    • CD1b
    • Lipid antigen
    • Mycolic acid
    • T cells
    • Tuberculosis

    Fingerprint

    Dive into the research topics of 'CD1b-mycolic acid tetramers demonstrate T-cell fine specificity for mycobacterial lipid tails'. Together they form a unique fingerprint.

    Cite this