Direct presentation of nonpeptide prenyl pyrophosphate antigens to human γδ T cells

Abstract

Human Vγ2Vδ2⁺ T cells recognize mycobacterial non-peptide antigens, such as isopentenyl pyrophosphate, and their synthetic analogs, such as monoethyl phosphate, through a TCR-dependent process. Here, we examine the presentation of these antigens. Vγ2Vδ2⁺ T cells recognized secreted prenyl pyrophosphate antigens in the absence of other accessory cells but, under such conditions, required T cell-T cell contact. Recognition required neither the expression of classical MHC class I, MHC class II, or CD1a, CD1b, and CD1c molecules, nor MHC class I or class II peptide loading pathways. Fixed accessory cells also presented the prenyl pyrophosphate antigens to γδ T cells. Thus, in contrast with the presentation of conventional peptide antigens, protein antigens, and superantigens to αβ T cells, prenyl pyrophosphate antigens are presented to γδ T cells through a novel extracellular pathway that does not require antigen uptake, antigen processing, or MHC class I or class II expression. This pathway allows for the rapid recognition of bacteria by γδ T cells and suggests that γδ T cells play a role in the early response to bacterial infection.