CLONAL SPECIFICITY OF HUMAN GAMMA-DELTA-T-CELLS - V-GAMMA-9+ T-CELL CLONES FREQUENTLY RECOGNIZE PLASMODIUM-FALCIPARUM MEROZOITES, MYCOBACTERIUM-TUBERCULOSIS, AND GROUP-A STREPTOCOCCI

Peripheral blood gammadelta T cells expressing a Vgamma9/Vdelta2 T-cell receptor are stimulated by killed bacteria including Mycobacterium tuberculosis (m.tb.) and group-A streptococci (strep A). In addition, recent data indicate that Vgamma9/Vdelta2 T cells from unexposed individuals also respond to Plasmodium falciparum (P. falcip.) merozoites. Here we analyzed the reactivity to these ligands of 23 Vgamma9/Vdelta2,3 Vgamma9/Vdelta1, and 4 Vgamma9-/Ndelta1 clones derived from 8 healthy individuals after phytohemaggltitinin stimulation of cell sorter-selected gammadelta T cells. Upon restimulation in the presence of irradiated antigen-presenting cells, the majority Of Vgamma9/Vdelta2 clones recognized m.tb. and strep A (but not strep D), and about one third of the clones also recognized P. falcip. Some clones, however, recognized only one or two of the tested ligands, and 4 Vgamma9/Vdelta2 clones did not react at all. Interestingly, 2 of 3 Vgamma9/Vdelta1 clones proliferated in response to m.tb., P. falcip., strep A and strep D, while Vgamma9-/Vdelta1 clones were not activated by any of the tested ligands. Nucleotide sequence analysis indicated a broad diversity of Vgamma9 N regions in Vgamma9/Vdelta2 clones. At the clonal level, our results demonstrate that individual Vgamma9/Vdelta2 T cells can recognize m.tb., strep A, as well as P. falcip.-infected erythrocytes, with no influence of the expressed Vgamma9 N region.