Conservation of Nonpeptide Antigen Recognition by Rhesus Monkey V 2V 2 T Cells

We have previously found that monkey V 2V 2 T cells mount adaptive immune responses in response to Mycobacterium bovis bacillus Calmette-Guérin infections. We have now analyzed rhesus monkey T cell responses to nonpeptide Ags and superantigens. Like human V 2V 2 T cells, rhesus monkey T cells are stimulated when exposed to prenyl pyrophosphate, bisphosphonate, and alkylamine Ags. Responsiveness was limited to T cells expressing V 2V 2 TCRs. Rhesus monkey V 2V 2 T cells also responded to the superantigen, staphyloccocal enterotoxin A. Sequencing of the rhesus monkey V 2V 2 TCR revealed a strong sequence homology to human V 2V 2 TCR that preserves important sequence motifs. Moreover, chimeric TCRs that pair human V 2 with monkey V 2 and monkey V 2 with human V 2 retain reactivity to nonpeptide Ags and B cell lymphomas. A molecular model of the rhesus monkey V 2V 2 TCR has a basic region in the complementarity-determining region 3 binding groove that is similar to that seen in the human V 2V 2 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 T cell Ag responses. The Journal of Immunology, 2003, 170: 3696–3706.