Nomenclature for T-cell receptor (TCR) gene segments of the immune system. WHO-IUIS Nomenclature Sub-Committee on TCR Designation.

Nomenclature for T-cell receptor (TCR) gene segments of the immune system* WHO-IUIS Nomenclature Sub-Committee on TCR Designation1 The recommended procedures and criteria for T-cell receptor (TCR) designations are described. The officially adopted designations are for the TCR A, B, D and G loci and for V, D, J and C segments. Principles of TCR nomenclature The following principles and criteria should be observed. (1) The intention is to develop a simple set of rules that can be applied to all TCR V, D, J and C loci and which are consistent with current trends in gene mapping nomenclature. (2) The nomenclature should be applicable to all species and to systems characterized at any level from the first sequence to full mapping. (3) To satisfy (2), the official name should not contain detailed information about gene order, pseudogenes, cDNA or genomic sequence, and the productive or non-productive nature of poly- morphisms. Such additional information should be in parentheses after the official name. (4) Gene segments should be named only when a full cDNA or genomic sequence is available. Naming is at the level of gene segments but data from the cDNA sequence may be used since for most genes only the cDNA sequence is available. A name for the rearranged gene product should be assembled from the loci names (see page 114, TCRD). (5) The locus names (A, B, G, D) and genetic elements (V, D, J, C) are self-explanatory. S refers to * This article was drafted by a group of experts working under the auspices of the International Union of Immunological Socie- ties (IUIS) and has been approved by the Nomenclature Com- mittee of IUIS. Requests for reprints and all correspondence should be addressed to the Chairman of the IUIS Nomenclature Committee, Professor Michel Kazatchkine, Unite d'Immunologie, H6pital Broussais, 96 rue Didot, 75014 Paris, France. A French translation of this Terminology Note will appear in a later issue of the Bulletin. Members of the Nomenclature Sub-Committee: A.F. Williams (United Kingdom) (Chairman), J.L. Strominger (USA) (Co- Chairman), and J. Bell (United Kingdom) (Co-Chairman), T.W. Mak (Canada), J. Kappler (USA), P. Marrack (USA), B. Arden (Germany), M.P. Lefranc (France), L. Hood (USA), S. Toneqawa (USA), and M. Davis (USA). Standing Committee on TCR Designation: T.W. Mak (Chairman), Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, Canada, and B. Arden, Paul Ehrlich Institute, Langen, Germany. Reprint No. 5362 gene segments and is used to enumerate and distinguish subfamily members. The TCR A and D V-segments present a problem since the same V region can be used for A or D TCR chains. In the present proposal one set of names is given for all A and D V-genes; the term A or D or both can be used in the name depending on whether the context is for TCR alpha or delta chains. Thus one might use TCRAV I S1 or TCRDV1 S1 or TCRADV1 S1 for the same V-gene in different contexts. This may seem unorthodox but once the A/D rule is known there is no problem since there will never be two A/D V-genes with the same V-S- name. The numbering of the few V-genes used mainly or exclu- sively in delta TCRs begin with 101, i.e., VIOlSI, V102S1, etc., allowing identification of unique delta families. (6) An asterisk (*) will separate alleles from loci, consistent with gene mapping rules. Nomenclature of human TCR gene segments The officially adopted designations for TCRA, TCRB, TCRG, TCRD (no hyphen separates TCR from A, B, G or D) loci are described below. (1) TCRA TCRAV1SI Distinct loci but these members TCRAV1S2 are of the same family, where S TCRAV1S3 refers to family member. See note 1 (Annex). TCRAV2S1 Second family. TCRADV 1S1 When the V region can be used by alpha or delta, A, D or AD can be used. See principle 5 (above). TCRAVlS1*1 Alleles at the same locus. See TCRAVlS1*2 notes 2 to 8 (Annex). Bulletin of the World Health Organization, 71 (1): 113-115 (1993) 113 WHO-IUIS Nomenclature Sub-Committee TCRAJISI S2 To designate J region families and their members. TCRAC1 *1 To designate AC locus. For AC *2 alleles if found. Further description, when available, could be pro- vided in parentheses. See note 5 (Annex). (2) TCRB TCRBV1S1 BV1S2 BV2S I *1 *2 *3 TCRBD1 TCRBD2 Exactly as for TCRAV. If alleles are found. For the 2 D loci. *1 If alleles are found. *2 TCRGC1 GC2*1 *2 *3 (4) TCRD TCRDVIO1S1 TCRADV1O1S1 TCRDVlOlS2 *1 *2 TCRDD1 TCRDD2 TCRDD3 *1 *2 For alleles of the 2nd GC seg- ment. As for the AV segments or with the 101 etc. names. See principle 5 (above). Where the sequence used in both alpha and delta AD can be used. To be added if alleles are found. For the D region genomic seg- ments. See note 10 (Annex). For the J region loci. See note 9 (Annex). If alleles are found. For the two BC loci For the V family with multiple segments. For all of the other segments including pseudogenes. See note 4 (Annex). To be added if alleles are found. To be added if alleles are found. TCRDJ I S1 TCRDJ1S2 TCRDJ2S 1 TCRDC1 For the 3 J segments. *1 For alleles as before. *2 For the only DC segment. Name for a rearranged gene product A complete name for a rearranged TCRA gene (for example) could be: TCRAVlSlJlS2Cl. Various shorthand versions could be used within a paper after the first complete naming: VlSlJlS2C1 or VlSlJ1S2 or VAlSlJlS2 or VAlSI or VA1.I or VB2S2JlS2 (for a TCRB gene) or VB2S2 or VB2.2 i.e., in a paper this last abbreviation would describe TCRBV2S2JlS2Cl (thereafter called VB2S2 or VB2.2). WHO Bulletin OMS. Vol 71 1993 TCRBJlSl TCRBJ1S2 TCRBJ1S3 TCRBJ2S 1 TCRBJ2S2 TCRBJ2S3 *1 *2 TCRBC 1 TCRBC2 (3) TCRG TCRGV1S1 S2 TCRGV2S 1 *1 *2 TCRGJ1SI TCRGJ1S2 TCRGJ1S3 TCRGJ2S 1 *1 *2 Nomenclature for TCR gene segments Annex Notes (1) Criteria for distribution to families have been given detailed consideration and will be in- cluded in a forthcoming publication. (2) Alleles should only be named if it is certain they are true alleles. If it is possible that they are pseudoalleles (product of a distinct locus), then they should be initially named as a family member but product of a distinct locus, e.g., AVlSI, AV1S2, AV1S3, etc. When proven to be truly allelic, the designation can be changed, e.g., AVlS3 could be changed to AVlS1*2 if it were allelic to AVlS1*1. Alleles are defined at the nucleic acid level. (3) Care must be taken to avoid using N addition nucleotides to designate a V, D or J segment as an allele. (4) If two identical sequences exist at different loci, these could bear the same name but be dis- tinguished by a or b after the name, i.e. TCRAV1Sl*la or TCRAVlSl*lb. (5) At the end of the official nomenclature a paren- thesis after the official name would contain information about: (a) gene order (b) pseudogenes (c) orphon genes (d) nonproductive substitutions (e) tentative designation (23) (P) (0) (N) (T) (5a) The gene order would require complete genomic mapping of a complex and would also address duplicate genes. (5b) Pseudogenes may be shown as a P after the official name. P would only be used when the sequence indicating a functional TCR could not be formed using this segment (e.g., frame shift from a single base deletion, stop codon, loss of an essential amino acid, etc.); i.e., TCRAVlS3*1P. (5c) For example, a processed pseudogene. Similarly, additional information about loci mapping outside the complex could be denoted by the letter 0 (orphon). (5d) An allelic nucleotide substitution that does not result in an amino acid change. (5e) When an incomplete sequence is obtained and clearly represents a new gene segment, it can be designated as tentative (T). This designation can be removed when the sequence is completed. For example: TCRAV I S 1* 1(43, P) Representing in or- der the locus num- ber from the C re- gion, in this case a pseudogene. or TCRAVlS1*2(43,N) In this case a non- productive allelic variant. or TCRAV1S7(0) An orphon gene. (6) Where the allelic polymorphism is the deletion of a gene, this could be designated by VlSl*O. (7) In order to be assigned a name, the sequence would have to be referenced (published or in press). Once the nomenclature is introduced and accepted, then all new sequences should be submitted to the Standing Committee by authors and/or editors for naming prior to publication (as is now done in the HLA field). (8) It would be difficult to insist that a cell line be deposited and available for verification (as is done for HLA alleles) because many TCR sequences are derived from factor-dependent lines (some easily lost) by PCR (polymerase chain reaction), etc. There does not seem to be an easy way to deal with this problem. (9) The J region loci are classed according to geno- mic localization, not sequence similarity. This is the one exception with the rest of the nomen- clature. (10) Where multiple D segments are used in the transcript, this can be expressed as follows: TCRDV 1 S2D2D3J2C 1. WHO Bulletin OMS. Vol 71 1993 115