Soluble MHC Molecules as T Cell Staining Reagents

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 cells^{4, 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.

References

1. Doherty, P.C. (1998) Science 280:227.
2. McCluskey, J. et al. (1988) J. Immunol. 141:1451.
3. Godeau, F. et al. (1992) J. Biol. Chem. 267:24223.
4. Altman, J.D. et al. (1998) Science 274:94.
5. Ogg, G.S. et al. (1998) Science 279:2103.
6. Goldstein, J.S. et al. (1998) J. Immunol. 160:3180.