Missing: A diagnostic technique to enumerate antigen-specific T cells

T lymphocytes are responsible for immune responses against pathogens, immune surveillance against cancer and maintenance of tolerance to self. While techniques available to detect antigen-specific T cells have been well described, there is a missing technique in our repertoire. While fluorescent multimers can be used for limited research applications, there is no existing technique suitable for detection of antigen-specific T cells in a diagnostic setting. The absence of such a technology has inhibited the search for “correlates of protection” against infectious, autoimmune or malignant disease. This critical review of existing methods will highlight the limitations of the data on which our current understanding of the immune system is based, in an effort to stimulate development of improved techniques.