Tetramer

A tetramer is a protein with four subunits (tetrameric). There are homo-tetramers (all subunits are identical) such as glutathione S-transferase or single-strand binding protein, dimers of hetero-dimers such as haemoglobin (a dimer of an alpha/beta dimer), and hetero-tetramers, where each subunit is different.

In Immunology, MHC tetramers can be used to quantitate numbers of antigen-specific T cells (especially CD8+ T cells). MHC tetramers are based on recombinant class I molecules that, through the action of bacterial BirA, have been biotinylated. These molecules are folded with the peptide of interest and β2M and tetramerized by a fluorescently labeled streptavidin. (Streptavidin binds to four biotins per molecule.) This tetramer reagent will specifically label T cells that express T cell receptors that are specific for a given peptide-MHC complex. For example, a Kb/FAPGNYPAL tetramer will specifically bind to Sendai virus specific CTL in a C57BL/6 mouse. Antigen specific responses can be measured as CD8+, tetramer+ T cells as a fraction of all CD8+ lymphocytes.

The reason for using a tetramer, as opposed to a single labeled MHC class I molecule is that the tetrahedral tetramers can bind to three TCRs at once, allowing specific binding in spite of the low (10-6 molar) affinity of the typical class I-peptide-TCR interaction.MHC Class II tetramers can also be made although these are more difficult to work with practically.