Application of tetramer technology in studies on autoimmune diseases

Autoreactive T cells are thought to play a role in the immunopathogenesis of autoimmune diseases. Analysis of such cells had long been hampered by lack of suitable assays. Recently developed tetramer technology is based on the recognition of specific peptide–MHC complex by T cell receptor and on the increased binding affinity of multimerized peptide–MHC complex. MHC class I and class II tetramers can be used to detect autoreactive CD4+ and CD8+ T cells, while nonclassical MHC (such as CD1d) tetramer can be used to detect other T cell groups, for example natural killer T cells. Tetramer technologies enable direct quantitation of autoreactive T cells in blood and affected tissues. It is also possible to carry out phenotypic and functional characterization of specific T cells on a single cell basis by using tetramers. Of special interest, in situ tetramer staining has the great potential of analyzing autoreactive T cells in their cellular environments. Utilization of tetramers in studies of autoreactive T cells is expected to generate important information regarding the role of such cells in the underlying mechanisms of autoimmune diseases.