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T cell stimulation usually requires direct contact with viable antigen-presenting cells (APCs). However, we show here that small exosome-like membrane vesicles shed from APCs can be recognized by naïve CD8+ T cells in the absence of viable APCs. T cell antigen receptor-dependent binding of vesicles by CD8+ cells is MHC class I/peptide-specific and requires that the vesicles coexpress intercellular adhesion molecule 1 (ICAM-1, CD54), although not B7 (B7-1). In the absence of B7, T cell binding of vesicles is nonimmunogenic. By contrast, vesicles expressing both ICAM-1 and B7 are strongly immunogenic and cause purified APC-depleted CD8+ cells to mount peptide-specific proliferative responses and differentiate into effector cells.

Direct stimulation of naïve T cells by membrane vesicles from antigen-presenting cells: Distinct roles for CD54 and B7 molecules