Peripheral blood γδ T cells expressing a Vγ9/Vδ2 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 Vγ9/Vδ2 T cells from unexposed individuals also respond to Plasmodium falciparum (P. falcip.) merozoites. Here we analyzed the reactivity to these ligands of 23 Vγ9/Vδ2,3 Vγ9/Vδ1, and 4 Vγ9-/Vδ1 clones derived from 8 healthy individuals after phytohemagglutinin stimulation of cell sorter-selected γδ T cells. Upon restimulation in the presence of irradiated antigen-presenting cells, the majority of Vγ9/Vδ2 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 Vγ9/Vδ2 clones did not react at all. Interestingly, 2 of 3 Vγ9/Vδ1 clones proliferated in response to m.tb., P. falcip., strep A and strep D, while Vγ9-/Vδ1 clones were not activated by any of the tested ligands. Nucleotide sequence analysis indicated a broad diversity of Vγ9 N regions in Vγ9/Vδ2 clones. At the clonal level, our results demonstrate that individual Vγ9/Vδ2 T cells can recognize m.tb., strep A, as well as P. falcip.-infected erythrocytes, with no influence of the expressed Vγ9 N region.

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