Clonotypes

In the immune system, the T cells and B cells (or lymphocytes) recognize their targets by producing a large number of variable receptors, where the sequence diversity, not encoded directly in the germ line, originates through somatic recombination. Each B or T cell expresses only one receptor variant, and the collection of all the different receptors in a cell population is called a repertoire. Once the somatic recombination is done, the receptor is transmitted to daughter cells across divisions, and the collection of cells expressing the same receptor, and by extension the receptor itself, is called a clonotype.

The processus of somatic recombination assembles a mature gene from arrays of segments on the genome. The junction between the N-terminal V and the downstream J segments, with the possible inclusion of a D segment in the case of the T cell receptor β chain and the immunoglobulin heavy chain, is called the complementarity determining region 3 (CDR3) and is one of the key contact points with the antigen.

In clonotypeR, we define clonotypes as unique combinations of V, CDR3 and J segments at the nucleotide or protein level. The V and J segments are encoded in the genome and are therefore called by their name, and the CDR3 region is identified by its sequence. For instance, each of the following lines define a different clonotype, not considering synonymous differences in the DNA sequence.

TRAV14N-1_14D-1 AASVSGYQNFY     TRAJ49
TRAV14N-1_14D-1 AASALYNAPR      TRAJ43
TRAV14D-3/DV8   AGLASSSFSKLV    TRAJ50

We use as boundaries between the V, CDR3 and J segments the conserved cystein and the FGxG motif, which we do not include in the CDR3.