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

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.

Effect of sea cucumber peptides on the immune response and gut microbiota composition in ovalbumin-induced allergic mice

“…CD4+ and CD8+ T cells are key links to immunoregulation in organisms. 34 CD8+ T cells are immune effector cells and responsible for the removal of target cells through a direct killing effect. 35 CD4+ T cells mainly consist of T-helper (Th) cells Th1, Th2, and Th17, and regulatory T-cells (Treg), which could be induced by different commensal microbiota.…”

Effect of Mycolic Acids on Host Immunity and Lipid Metabolism

“…Our research demonstrates that T cell recognition of GMM relies on T cell receptors (TCRs) and exhibits remarkable specificity toward the native GMM structure produced by mycobacteria. This suggests that T cells possess the capability to intricately discern the hydrophilic cap of an antigen, potentially functioning as a classical TCR epitope by direct interaction with the TCR variable region [ 51 , 52 ]. In addition, GMM must be synthesized with glucose provided by mammals, which means that GMM production can be used as a good indicator of local invasion of mycobacteria, and its detection by the host immune system is helpful for effective monitoring of mycobacterial infection [ 53 ].…”

Comparative immune responses toMycobacterium tuberculosisin people with latent infection or sterilizing protection

“…Of special interest was a population of CD8+GMM+GranzB+ Tconv that was not part of the prespecified manual gating but was identified by the Phenograph cluster analysis. This cell subset, which has only recently been described, was found in people with active TB, in whom CD8+GMM+ T cells displayed upregulated cytotoxic transcription profiles[56]. The authors concluded that this cell subset may contribute to the clearance of Mtb -infected host cells.…”