Notes on Tetramer Nomenclature

When you are reporting results from tetramer stains, how should you refer to the tetramer you used?

Many approaches have been used, and there is no perfect way to do it. Usually, the trade off is between a nomenclature that specifices the reagent completely and unambiguously—but which is therefore unwieldly—and shorthand nomenclatures that are ambiguous and that may "break" over time as new epitopes are described. The approach we usually use is a compromise.

Considerations in Tetramer Nomenclature

  1. There are three components that determine the specificity of a classical class I MHC tetramer: the heavy chain, the beta-2-microglobulin, and the antigenic peptide.
  2. The species of the b2m subunit is not usually specified in most tetramer nomenclatures. The beta-2-microglobulin component can be matched to the species of the heavy chain, but more often than not, we use human beta-2-microglobulin, even when the heavy chain is from species such as the mouse.
  3. Naming of the heavy chain is usually straightforward. For human reagents, the "HLA" prefix is often eliminated, and alleles are referred to by shorthand names, such as A2, B27, B57, etc. This can be done for other primate species as well, though it is not uncommon to include prefixes such as "Mamu" for rhesus macaque reagens and "Patr" for chimpanzee reagents. For mouse reagents, heavy chains are usually referred to with nomenclatures such as D(b), K(b), L(d), etc.
  4. From the beginning, naming of the peptide has often been haphazard and has been done carelessely. For example, in the first tetramer paper, we referred to one reagent as "A2/gag". In the context of the original publication, it was obvious that this referred to the HIV gag protein, and most experts in the field understood this to refer to the immunodominant SLYNTVATL epitope that started at the 77'th amino acid of the gag protein. However, in hindsight, it is possible that other A2-restricted epitopes might be found in gag, making our original nomenclature ambiguous. As a consequence, we now favor a nomenclature such as "A2/HIV.gag.77-85", which indicates the pathogen and protein source of the epitope, as well as it's position in the sequence. Of course, even this nomenclature has its faults, as it's long and doesn't account for possible mutations, etc., but we believe it's the best of a bad lot.