Direct presentation of nonpeptide prenyl pyrophosphate antigens to human gamma delta T cells

Immunity. 1995 Oct;3(4):495-507. doi: 10.1016/1074-7613(95)90178-7.


Human V gamma 2V delta 2+ T cells recognize mycobacterial nonpeptide 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. V gamma 2V delta 2+ 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 gamma delta T cells. Thus, in contrast with the presentation of conventional peptide antigens, protein antigens, and superantigens to alpha beta T cells, prenyl pyrophosphate antigens are presented to gamma delta 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 gamma delta T cells and suggests that gamma delta T cells play a role in the early response to bacterial infection.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigen Presentation*
  • Antigens, Bacterial / immunology*
  • Cell Line
  • Diphosphates / immunology*
  • Humans
  • Lymphocyte Activation
  • Lymphocyte Cooperation
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Signal Transduction
  • T-Lymphocytes / immunology*


  • Antigens, Bacterial
  • Diphosphates
  • Receptors, Antigen, T-Cell, gamma-delta