Human tetramers

TCRs recognize and bind to complexes composed of MHC molecules and specific peptides expressed on the surface of antigen-presenting cells. While it was once believed that antigen-specific T cells could be detected using soluble MHC/peptide complexes, monomeric MHC/peptide complexes proved to be impractical due to their instability and low affinity to the TCR. To overcome this difficulty, MHC/peptide monomers are biotinylated and tetramerized with streptavidin to maintain stable binding to multiple TCR, enabling MHC/peptide tetramers to be used as detection tools. MHC tetramers are labeled with fluorescent molecules including phycoerythrin (PE), allophycocyanin (APC), or Brilliant Violet 421 (BV421) and thus allow detection of antigen-specific T cells by flow cytometry or fluorescence microscopy.