A clonotype nomenclature for T cell receptors

Abstract

T cell receptor (TCR) nucleotide sequences are often generated during analyses of T cell responses to pathogens or autoantigens. The most important region of the TCR is the third complementarity-determining region (CDR3) whose nucleotide sequence is unique to each T cell clone. The CDR3 interacts with the peptide and thus is important for recognizing pathogen or autoantigen epitopes. While conventions exist for identifying the various TCR chains, there is a lack of a concise nomenclature that would identify both the amino acid translation and nucleotide sequence of the CDR3. This deficiency makes the comparison of published TCR genetic and proteomic information difficult. To enhance information sharing among different databases and to facilitate computational assessment of clonotypic T cell repertoires, we propose a clonotype nomenclature. The rules for generating a clonotype identifier are simple and easy to follow, and have a built-in error-checking system. The identifier includes the V and J region, the CDR3 length as well as its human or mouse origin. The framework of this naming system could also be expanded to the B cell receptor.

Fig. 1

An example of TCR β-chain clonotype identifier. The BV and the BJ regions are fully identified. The single-letter -code amino acid translation is shown below the nucleotide sequence. The bold uppercase letters represent the conserved amino acids from the V (C) and from the J (FG). The amino acids that are not completely encoded by the germline, which are predominantly encoded by the NDN, are also in uppercase (IRSS). Below the NDN-encoded amino acids is the codon ID for each of them as assigned from the Table 1. The bold underlined lowercase letters represent the last amino acid that is completely encoded by the V gene (s) and the first amino acid that is completely encoded by the J region (y). The clonotype identifier takes the uppercase NDN amino acids and flanks them with the lowercase V and J encoded amino acids. This is followed by the codon ID for the uppercase NDN sequence. The V and J chains are next identified. Finally, the length of the CDR3 is determined by counting the number of amino acids between the uppercase C and uppercase FG. This count is shown in the top line

Fig. 2

Deriving the nucleotide sequence of the CDR3 by decoding the clonotype TCR β-chain identifier. The genomic sequence of the TCRV gene (AV38S2) is obtained and the positions of the amino acids lined up with a length ruler starting with the position immediately after the conserved cysteine. The TCRJ gene (AJ53) is then placed so that the last amino acid before the conserved FG lines up with the end of length ruler. The two lowercase letters “r” and “s” in the name identify the last V and first J position encoded by germline. This leaves one position to be filled by the N nucleotides and this is the threonine represented as “T” in the clonotype name. The codon table shows that codon 4 for T is ACG, and the only way that the T can be encoded is that the initial nucleotide, A, is from the V germline sequence and the rest of the sequence is N derived