A NOVEL NUCLEOTIDE-CONTAINING ANTIGEN FOR HUMAN BLOOD GAMMA-DELTA T-LYMPHOCYTES

The stimulation of human gamma delta T cells by mycobacteria occurs th rough recognition of our distinct nonpeptide phosphorylated antigens t ermed TUBag1-4. Among these latter, TUBag4 has already been biochemica lly characterized as a gamma-X derivative of 5'-deosythymidine triphos phate (Constant, P., Davodeau, F, Peyrat, M. A.: Poquet, Y., Puzo, G,, Bonneville, M. and Fournie, J.-J., Science 1991. 264: 267). However, despite chemical synthesis of weakly stimulatory nucleotide-containing analogs, these mycobacterial compounds remained the sole nucleotide-c ontaining antigens actually isolated from natural sources, Here, we pr esent the complete isolation of the TUBag3 antigen from Mycobacterium fortuitum and demonstrate that this nonpeptide molecule contains a 5'- UTP nucleotide moiety. On selected V gamma 9/V delta 2 clones, T cell responses can be triggered with nanomolar concentrations of TUBag3, Li ke crude mycobacterial extracts, this purified nucleotide conjugate el icits a strong polyclonal response of gamma delta PBL from healthy don ors, Furthermore, we present evidence that this compound is distinct f rom the recently synthesized gamma-isopentenyl 5'-UTP, a nucleotide co njugate of isopentenyl pyrophosphate that was found to be stimulatory for human gamma delta T cells (Tanaka, Y., Morita, C. T., Tanaka, Y., Nieves, E., Brenner, M. B, and Bloom, B. R., Nature 1995. 375: 155). S ince it appears that both mycobacterial nucleotide antigens are molecu les structurally related to peculiar precursors of nucleic acid synthe sis, we propose that TUBag-reactive T cells might be specifically devo ted to surveillance of proliferating cells.