Conservation of nonpeptide antigen recognition by rhesus monkey Vγ2Vδ2 T cells

Abstract

We have previously found that monkey Vγ2Vδ2+ T cells mount adaptive immune responses in response to Mycobacterium bovis bacillus Calmette-Gu?rin infections. We have now analyzed rhesus monkey γδ T cell responses to nonpeptide Ags and superantigens. Like human Vγ2Vδ2+ T cells, rhesus monkey γδ T cells are stimulated when exposed to prenyl pyrophosphate, bisphosphonate, and alkylamine Ags. Responsiveness was limited to γδ T cells expressing Vγ2Vδ2 TCRs. Rhesus monkey Vγ2Vδ2+ T cells also responded to the superantigen, staphyloccocal enterotoxin A. Sequencing of the rhesus monkey Vγ2Vδ2 TCR revealed a strong sequence homology to human Vγ2Vδ2 TCR that preserves important sequence motifs. Moreover, chimeric TCRs that pair human Vγ2 with monkey Vδ2 and monkey Vγ2 with human Vδ2 retain reactivity to nonpeptide Ags and B cell lymphomas. A molecular model of the rhesus monkey Vγ2Vδ2 TCR has a basic region in the complementarity-determining region 3 binding groove that is similar to that seen in the human Vγ2Vδ2 TCR and preserves the topology of the complementarity-determining region loops. Thus, recognition of nonpeptide prenyl pyrophosphate, bisphosphonate, and alkylamine Ags is conserved in primates suggesting that primates can provide an animal model for human γδ T cell Ag responses.