Phosphate is essential for stimulation of Vγ9Vδ2 T lymphocytes by mycobacterial low molecular weight ligand

Abstract

T lymphocytes are divided into two subsets which express different T cell receptor heterodimers. In the peripheral blood of healthy individuals, the majority of T cells express the alpha/beta T cell receptor (> 90%) while a minority have the gamma/delta T cell receptor (< 10%). The gamma/delta T cells of adults use preferentially the V gamma 9V delta 2 chain combination. Although the stimulation requirements for gamma/delta T lymphocytes are still undetermined, it has been reported that gamma/delta T cells are not only stimulated, like alpha/beta T cells, by conventional protein antigens and superantigens, but also by unusual ligands. Mycobacteria selectively stimulate V gamma 9V delta 2 T cells, and a nonproteinacious low molecular weight fraction of 1-3 kDa has been identified as the tentative active component. Here, we confirm the nonproteinacious nature of this ligand, and show that it is comprised of unusual carbohydrate and phosphate. Importantly, cleavage of the terminal phosphate by alkaline phosphatase completely abrogates the stimulatory activity of the low molecular weight ligand for V gamma 9V delta 2 T cells. Even mycobacterial whole lysate loses its stimulatory activity, for this T cell subset, after dephosphorylation with alkaline phosphatase. These findings identify phosphocarbohydrates as a novel molecular entity with selective stimulatory activity for a defined T cell subset.

Differential Effects of Control and Antigen-Specific T Cells on Intracellular Mycobacterial Growth

“…3B). In addition, phosphoantigen-responsive human ␥␦ T cells are stimulated by mycobacterial components (29,34,40,46,47,50) and increased ␥␦ T-cell responses have been detected in partially resistant, healthy PPD-positive and BCG-vaccinated persons (19,31). We now present data that ␥␦ T cells expanded with live BCG (Table 1) or M. tuberculosis lysate (data not shown) were the most potent inhibitors of intracellular mycobacteria in our assay system and therefore could be important for vac- cine-induced TB immunity.…”

Host Responses and Antigens Involved in Protective Immunity to Mycobacterium tuberculosis

“…Recent evidence strongly in favour of the latter observation indicates that the ligands recognized are phosphorylated nucleotide conjugates containing thymidine and with an estimated molecular mass of 500-600 daltons [88]. The phosphate component seems to be essential and cleavage completely abrogates the stimulatory activity for gd cells [89]. Another cell type represented in very low percentages is CD4 -, CD8 -but ab TCR + T cells.…”

γδ T lymphocyte responses to HIV

“…T cells) can respond to non-peptide antigens [60][61][62][63][64], it is possible that T lymphocytes may have an T cell-complementing function in immunosurveillance against various infectious agents, including HIV. …”