This technology "looks set to be the gold standard for quantifying virus-specific CD8+ T cells" is how Nobel laureate Peter C. Doherty described the revolutionary nature of soluble major histocompatibility complex (MHC) molecules as staining reagents for the identification of antigen-specific T cells.1 MHC glycoproteins are normally found as membrane-anchored molecules that coordinate communications between lymphoid cells. T cells respond specifically to cells that present fragments of infectious organisms bound to MHC molecules. Each clone of T cells has a T-cell receptor specific for a particular peptide bound to a particular MHC.
Until recently, the quantitation of antigen-specific T cells required difficult limiting dilution assays. Creative genetic engineering led to a novel application for MHC molecules. Early work demonstrated the ability to isolate biologically active soluble MHC molecules.2, 3 More recently, fluorescently labeled peptide-loaded soluble MHC molecules were useful in the quantitation of HIV-specific CD8+ T cells4, 5 and as mitogenic reagents.6
Use of MHC molecules as cell-staining reagents overcomes the inability to detect antigen-specific T cells that have low proliferative capacity in limiting dilution assays, and they provide the ability to monitor a patient's immune status during the course of the disease or following antigen specific vaccination.