Label-free Electronic Detection of the Antigen-Specific T-Cell Immune Response

Citations Over TimeTop 10% of 2008 papers

Abstract

Detection of antigen-specific T-cells is critical for diagnostic assessment and design of therapeutic strategies for many disease states. Effective monitoring of these cells requires technologies that assess their numbers as well as functional response. Current detection of antigen-specific T-cells involves flow cytometry and functional assays and requires fluorescently labeled, soluble forms of peptide-loaded major histocompatability complexes (MHC). We demonstrate that nanoscale solid-state complementary metal-oxide-semiconductor (CMOS) technology can be employed to allow direct, label-free electronic detection of antigen-specific T-cell responses within seconds after stimulation. Our approach relies on detection of extracellular acidification arising from a small number of T-cells (as few as approximately 200), whose activation is induced by triggering the T-cell antigen receptor. We show that T-cell triggering by a nonspecific anti-CD3 stimulus can be detected within 10 s after exposure to the stimulus. In contrast, antigen-specific T-cell responses are slower with response times greater than 40 s after exposure to peptide/MHC agonists. The speed and sensitivity of this technique has the potential to elucidate new understandings of the kinetics of activation-induced T-cell responses. This combined with its ease of integration into conventional electronics potentially enable rapid clinical testing and high-throughput epitope and drug screening.

Related Papers

• → T Cell Receptor Signaling Is Limited by Docking Geometry to Peptide-Major Histocompatibility Complex(2011)261 cited
• → Hard wiring of T cell receptor specificity for the major histocompatibility complex is underpinned by TCR adaptability(2010)114 cited
• → Current status and future challenges in T-cell receptor/peptide/MHC molecular dynamics simulations(2015)56 cited
• → Molecular modeling of a T-cell receptor bound to a major histocompatibility complex molecule: Implications for T-cell recognition(1995)12 cited
• → Engagement of a T cell receptor by major histocompatibility complex irrespective of peptide(1997)7 cited