MHC multimers: expanding the clinical toolkit.

T cell recognition of specific antigen is initiated by the interaction between TCR molecules and peptide–MHC complexes (pMHC) expressed on the surface of antigenpresenting cells. Soluble pMHC molecules can substitute as ligands in this interaction, binding specifically to T cells expressing the appropriate TCR. Because the monomeric interaction of TCR–pMHC is of low avidity [1–6], multimerization of the pMHC complex facilitates the binding reaction, and a large number of studies have now been performed in which pMHC multimers are used to detect and characterize specific T cells in patients and normal individuals. This technology, commonly referred to as “MHC tetramers,” was originally developed for the analysis of class I restricted CD8 T cells, in which the TCR recognizes a MHC class I–antigen complex [7]. Similar technology has been used for class I recognition by NK receptors [8–10], for CD1 recognition by NKT cells [11,12], for MIC recognition by -TCR molecules [13], and for recognition of the peptide–HLA class II complex by CD4 T lymphocytes in humans [14–19] and mice [20,21].