Nomenclature for clusters of differentiation (CD) of antigens defined on human leukocyte populations*

/ l rnmlnolol Bulletin ofthe World Health Organization, 62 (S): 809- 811 (1984) wcd' World Health Organization 1984 Nomenclature for clusters of differentiation (CD) of antigens defined on human leukocyte populations* IUIS-WHO NOMENCLATURE SUBCOMMITTEE1 Evaluation of 139 monoclonal antibodies detecting human leukocyte differentiation antigens during the First International Workshop on Human Leucocyte Differentiation Antigens in 1982 permitted the designation ofa nomenclaturefor the Clusters ofDifferen- tiation of antigens defined on human leukocyte populations. The general principles of this nomenclature, as well as the characteristics of thefifteen Clusters of Differentiation which have so far been defined, are presented. In November 1982, the results of the First Inter- national Workshop on Human Leucocyte Differen- tiation Antigens, sponsored by the International Union of Immunological Societies (IUIS), Institut national de la Sante et de la Recherche medicale (INSERM), the Medical Research Council, and WHO, were presented at a meeting held in Paris. The data from these common blind studies were collected by 55 research groups from 14 different countries for publication.a A total of 139 monoclonal antibodies were examined in immunofluorescence tests and the results expressed as a percentage of positive cells. The statistical analysis relied on the distances between antibodies. The distance between 2 antibodies for a given target cell type is the average of the absolute dif- ference between the reactivities of the 2 antibodies for all target cells of the type considered. Then cluster analysis of the matrix of distances between all pairs of antibodies and algorithmic computation permitted the definition of groups of antibodies that were similar, and those that were clearly different, on each type of target cell. The clusters of differentiation were then readily delineated from summing-up tables of groups of anti- * A French translation of this terminology note appears on pages 813-815. See pages 809-810 for the names of the members of this Committee. Requests for reprints should be sent to Dr S.F. Schlossman, 44 Binney Street, Boston, MA 02115, USA. a BERNARD, A. ET AL., ed., Leucocyte typing. Report of the First International Workshop on Human Leucocyte Differentiation Antigens. Heidelberg, Springer Verlag, 1984, pp. 9-143. bodies obtained for each target cell type; these clusters included the antibodies that always had very similar reactivities. Moreover, the confrontation between blind studies on the relative molecular mass ("molecular weight"), performed with the anti- bodies, and cluster analysis showed an almost perfect correspondence. These final clusters were termed clusters ofdifferentiation (CD) following the general recommendations (Table 1) adopted by the Nomen- clature Subcommittee, which were approved with no objections or comments from the 250 scientists (including most of the workshop participants) at the Paris meeting mentioned above. Both oral and written designations of the first eleven clusters (as shown in Table 2) were officially adopted by the Nomenclature Subcommittee which met in Kyoto in August 1983 during the Vth Inter- national Congress of Immunology. The new nomenclature relies on a simple, un- ambiguous, and adaptable system, thus avoiding the major difficulties in communication which had pre- viously arisen from the multiplicity of nomenclatures used. It is the one that should now be followed. * * * A. Bernard, Institut Gustave Roussy, Villejuif, France I. Bernstein, Fred Hutchison Cancer Research Center, Seattle, WA, USA 461 -809- HUMAN LEUKOCYTE DIFFERENTIATION ANTIGENS L. Boumsell, Hopital Saint-Louis, Paris, France J. Dausset, Hopital Saint-Louis, Paris, France R. Evans, Sloan Kettering Research Institute, New York, NY, USA J. Hansen, Fred Hutchison Cancer Research Center, Seattle, WA, USA B. Haynes, Duke University Medical Center, Durham, NC, USA J. Kersey, University Hospitals and Clinics, Minneapolis, MN, USA W. Knapp, Institut fur Immunologie, Vienna, Austria A. McMichael, John Radcliffe Hospital, Oxford, England C. Milstein, MRC Laboratory of Molecular Bio- logy, Cambridge, England E. Reinherz, Dana Farber Cancer Center, Boston, MA, USA R.E. Ritts, Mayo Research Foundation, Rochester, NY, USA S.F. Schlossman, Dana Farber Cancer Center, Boston, MA, USA Table 1. Explanation of the nomenclature system for leukocyte differentiation antigens CD No. [cell, M.W.] name of monoclonal antibody CD: Cluster of differentiation. No. Here is given the number officially ascribed to the cluster." In square brackets: Cell: Typical cell of the particular CD, or cell type on which the relative molecular mass or "molecular weight" (M.W.) was determined. M.W.: "Molecular weight" or relative molecular mass of the antigen on the particular cell type, as determined on the specimen reduced in a strong denaturant. The M.W. is preceded by: gp: glycoprotein gI: glycolipid cho: carbohydrate When the M.W. is not known, the letter "u" (= unknown) is used in its place. After the brackets: The name of the particular monoclonal antibody is mentioned here. Example: CALLA," investigated by the monoclonal antibody J5 on non-T, non-B leukaemic cells, should be designated: CD10 lnT-nB, gplOO] J5 Oral designation should be limited to CD 10. Whenever definitive official recognition of a given CD cannot be achieved, but it is nevertheless felt that an official designation should be provisionally adopted, the CD could be termed CDw No. In Kyoto (August 1983), the Subcommittee officially recognized 1 1 CDs and provisionally termed 4 additional CDws. Their identity and designation are indicated in Table 2. " CALLA: the former common acute lymphoblastic leukaemia antigen. Table 2. Clusters of differentiation of human leukocyte differentiation antigens Cluster designation' Antibodies" Typical leukocyte subpopulations Leukocyte malignanciesc CD1 IThy, gp45,121 NA1/34, T6, M241, D47 Corticothymocytes Fewd T-ALL and T-LL CD2 IT, gp50l 9.6, Ti 1, 35.1 All T-cells forming E rosette Most d T-cell malignancies Cp3 IT, gpl 9-291 T3, UCHT 1, 89bl, 38.1 Mature T-cells Most T-CLL and CTCL Few T-ALL and T-LL CD4 IT, gp56-621 T4, Leu3a, 91 D6 Subset of T-cells Few T-ALL, somed T-CLL Mostly inducers Most CTCL CD5 IT, gp671 A50, 10.2, Ti, UCHT2, Pan T + subpopulation Most T-cell malignancies SC1, AMG4, T101, Cris 1, B-cells Some B-CLL H65, HH9 CD6 IT, gpl 201 12.1, T41 1, B614, Mature T + subpopulation Few T-ALL, most T-CLL and WT31, MBG6 B-cells CTCL. Some B-CLL CD7 IT, gp4l1 3A1, 4A, CL1.3 Pan T Most T-ALL, some T-CLL Few CTCL CD8 IT, gp32-331 Leu2a, T8, M236, 51.1, Subset of T-cells Few T-ALL and T-CLL UCHT4, 2D2, B9.4.1, Mostly cytotoxic/suppressor B9.3.1, B9.7.6, B9.2.4, B9.8.6, B9.11.10, B9.1.1, C10, T811 810 811HUMAN LEUKOCYTE DIFFERENTIATION ANTIGENS Table 2. - continued Cluster designation' Antibodies" Typical leukocyte subpopulations Leukocyte malignancies" CD9 [nT-nB, gp241 BA2, DU-ALL-1, FMC8, Monocytes Most nonT-nonB ALL SJ9A-4, WB3 Few B-CLL CD10 [nT-nB, gplOOJ J5, BA3, NL-1, 24.1, Pre-B cell Most nonT-nonB ALL VIL-Al Polymorphs CD1 1 IM, G, ul M01, B2.12, M522 Monocytes and granulocytes Some M4 and most M5 stages Some bone marrow cells of AML. Some CML CDw12 [M, G, ul 20.2, M67 Monocytes and granulocytes Few M4 and M5 stages of AML CDw13 [M, G, ul MY7, DU-HL60-4, MCS.2 Monocytes and granulocytes Most Ml and few M4 or M5 stages of AML. Some CML CDw14 IM, ul 20.3, 5F1, MOP15, M02, Monocytes Few M4 and some M5 stages MOS1, MY4, MOS39, TM 18, of AML MOP9, FMC1 7 CDw15 [G, ul 80H3, B13.9, MCS.1, 82H7 Granulocytes Most M4 and some M5 stages FMC1 2, FMC1 3, WM37, Some bone marrow cells of AML. Some CML DU-HL60-1, FMC10, WM27, WM30, Gl 120, TG8, WM38, TG1, DU-HL60-3, G2, B4.3, VIMD5, WM41, lGlO See Table 1. b List of antibodies in the cluster. Abbreviations used: ALL, acute lymphoblastic leukaemia LL, lymphoblastic lymphoma CLL, chronic lymphocytic leukaemia CTCL, cutaneous T-cell lymphoma AML, acute myeloblastic leukaemia CML, chronic myelogenous leukaemia. d Frequency of positive cases is indicated as: "few" for frequency of 10-39% "some" for frequency of 40-70% "most" for frequency of > 70% Bulletin de l'Organisation mondiale de la Sante, 62 (5): 813-815 (1984) X Organisation mondiale de la Sante 1984 Nomenclature des Classes de Differenciation (CD) des antigenes de surface definis dans les populations leucocytaires humaines* SOUS-COMITI IUIS-OMS DE NOMENCLATURE' L 'evaluation, lors du Premier Atelier international sur les antigenes de diffe'renciation des leucocytes humains (1982), de 139 anticorps monoclonaux assurant la de'tection de ces antigenes, a permis defixer une nomenclature des classes de diff6renciation des antigenes d6finis dans les populations leucocytaires humaines. Les principes generaux de cette nomenclature sont presentes, ainsi que les caracte'ris- tiques des quinze classes de differenciation de6finies a ce jour. En novembre 1982, les resultats du Premier Atelier international sur les antigEnes de differenciation des leucocytes humains (qui avait et patronne par l'Union internationale des Socite's d'Immunologie (IUIS), l'Institut national de la Sante et de la Recherche medicale (INSERM), le Medical Research Council (MRC) et l'OMS ont W presentes lors d'une reunion tenue A Paris. Ces resultats, provenant d'etudes concertees conduites en aveugle, avaient W obtenus par 55 6quipes de chercheurs de 14 pays diff6rents, en vue de leur publication.' Au total, 139 anticorps monoclonaux ont W examines en immunofluorescence, les resultats etant exprim6s sous forme du pourcentage de cellules positives. L'analyse statistique effectuee repose sur la "distance" des anticorps pris deux A deux, laquelle est 6gale A la moyenne de la valeur absolue des differences entre les pourcentages de cellules positives observ6es avec ces deux anticorps et pour les divers types de cellules cibles. Une analyse de classe, pratiquee, selon un algorithme determine, a partir de la matrice des distances entre tous les couples d'anticorps, a permis de definir des groupes d'anticorps semblables ou au contraire nettement diff6rents par leur comportement vis-a-vis de tel ou tel type de cellule cible. Des classes de differenciation ont alors pu etre facilement delimitees A partir de tableaux recapitu- latifs des groupes d'anticorps obtenus pour chaque * L'original, en anglais, de cette note terminologique figure aux pages 809-811. ' On trouvera aux pages 813-814 les noms des membres du Comit6. Les demandes de tir6s a part doivent etre faites aupr6s du Dr L. Boumsell, INSERM U93, H6pital Saint-Louis, 75010 Paris, France. a BERNARD A. ET AL., red., Leucocyte typing. Report of the First International Workshop on Human Leucocyte Differentiation Antigens. Heidelberg, Springer Verlag, 1984, pp. 9-194. type de cellule cible; ces classes regroupent les anti- corps qui se sont montres tres voisins dans tous les cas. Par ailleurs, on a v6rifi6, en rapprochant les etudes de masse moleculaire relative effectuees en aveugle au moyen des batteries d'anticorps et l'ana- lyse de classes ci-dessus, que leurs r6sultats se recou- paient presque parfaitement. Les classes finales ainsi d6finies ont ete qualifiees de Classes de Differen- ciation (CD), conformement aux recommandations generales (Tableau 1) qu'a adoptees le Sous-Comit6 de Nomenclature, en l'absence d'objections ou d'observations de la part des 250 chercheurs presents en seance pleniere (et reunissant la majorite des parti- cipants a l'Atelier). La designation des onze premieres classes (repro- duite au Tableau 2), tant par ecrit qu'oralement, a e officiellement adopt&e par le Sous-Comite de Nomenclature qui s'est r6uni a Tokyo en aofut 1983, en marge du Cinquieme CongrFs international d'Immunologie. La nouvelle nomenclature est fond6e sur un sys- teme simple, evolutif, sans ambigu-it ni rigidit6, et supprime donc les graves difficult6s de communi- cation qui decoulaient jusqu'ici de la multiplicite des nomenclatures en usage. C'est d6sormais la nomen- clature qu'il faut appliquer. * * A. Bernard, Institut Gustave Roussy, Villejuif, France I. Bernstein, Fred Hutchison Cancer Research Center, Seattle, WA, Etats-Unis d'Amerique L. Boumsell, Hopital Saint-Louis, Paris, France J. Dausset, Hopital Saint-Louis, Paris, France R. Evans, Sloan Kettering Research Institute, New York, NY, Etats-Unis d'Amerique 4462 -813- ANTIGENES DE DIFFIRENCIATION LEUCOCYTAIRES HUMAINES J. Hansen, Fred Hutchison Cancer Research Center, Seattle, WA, Etats-Unis d'Amerique B. Haynes, Duke University Medical Center, Durham, NC, Etats-Unis d'Amerique J. Kersey, University Hospitals and Clinics, Minneapolis, MN, Etats-Unis d'Amerique W. Knapp, Institut fuir Immunologie, Vienne, Autriche A. McMichael, John Radcliffe Hospital, Oxford, Angleterre C. Milstein, MRC Laboratory of Molecular Bio- logy, Cambridge, Angleterre E. Reinherz, Dana Farber Cancer Center, Boston, MA, Etats-Unis d'Amerique R.E. Ritts, Mayo Research Foundation, Rochester, NY, Etats-Unis d'Amerique S.F. Schlossman, Dana Farber Cancer Center, Boston, MA, Etats-Unis d'Amerique Tableau 1. Presentation du systeme de nomenclature applicable aux antigenes de differenciation des leucocytes CD N0 Icollule,.MM.1 nom de I'anticorps monoclonal CD: Classe de differenciation. NO: ce numero correspond a celui qui est officiellement attribue A la classe.' Entre crochets: Cellule: cellule typique de la CD particuliere ou type cellulaire ayant servi A la d6termination de la masse moleculaire relative (M.M.). M.M.: masse moleculaire relative de I'antigAne sur le type de cellule en cause, determin6e sur 1'6chantillon reduit dans un fort denaturant. La masse moleculaire est pr6c6d6e, selon le cas, de: gp pour glycoproteine, gl pour glycolipide, cho pour glucide (carbohydrate). Quand la M.M. n'est pas connue, elle est remplacee par la lettre u (unknown = innconnue). A la suite des crochets: On indiquera le nom de l'anticorps monoclonal de la classe, selon la preference personnelle de l'auteur. Exemple: dans le cas de CALLAb etudie a l'aide de l'anticorps monoclonal J5 sur des cellules leucemiques ni T- ni B, on utilisera par Acrit la dAsignation: CD10 InT-nB, gplOOJ J5 Oralement, on se contentera de parler de CD1 0. ' Quand il est impossible d'adopter definitivement une CD determinee mais qu'il semble neanmoins necessaire d'en fixer provisoirement la dAsignation officielle, cette CD sera qualifiee de CDw. A Kyoto (ao0t 1983), le Sous-Comite a officiellement reconnu 1 1 CD et il a provisoirement dAsignA 4 CDw. Leur identite et la dAsignation correspondante figurent au Tableau 2. b CALLA: Ancien "Common Acute Lymphoblastic Leukaemia Antigen". Tableau 2. Classes de diff6renciation des antigenes de diff6renciation des leucocytes humains Designation de la classe° Anticorpsb Sous-populations leucocytaires Proliferations leucocytaires typiques malignesc CD1 IThy, gp45,121 NA1/34, T6, M241, D47 CD2 IT, gp501 CD3 IT, gp19-291 CD4 IT, gp56-621 CD5 IT, gp671 CD6 IT, gpl 201 CD7 IT, gp4ll 9.6, Tl1, 35.1 T3, UCHT 1, 89bl, 38.1 T4, Leu3a, 91 D6 A50, 10.2, Ti, UCHT2, SCI, AMG4, T101, Cris 1, H65, HH9 12.1, T411, B614, WT31, MBG6 3A1, 4A, CL1.3 Thymocytes de la zone corticale Totalite des cellules T formant des rosettes E Cellules T matures Sous-population de cellules T, inductrices pour la plupart Ensemble des cellules T + sous- population de cellules B Cellules T matures + sous- population de cellules B Ensemble des cellules T Un petit nombred de T-ALL et de T-LL La plupartd des proliferations malignes A cellules T La plupart des T-CLL et des CTCL Un petit nombre de T-ALL et de T-LL Un petit nombre de T-ALL, quelquesd T-CLL La plupart des CTCL La plupart des proliferations malignes A cellules T Quelques B-CLL Un petit nombre de T-ALL, la plupart des T-CLL et des CTCL. Quelques B-CLL La plupart des T-ALL, quelques T-CLL Un petit nombre de CTCL 814 ANTIGENES DE DIFFERENCIATION LEUCOCYTAIRES HUMAINES 815 Tableau 2.- Suite Designation de la classea Anticorps" Sous-populations leucocytaires Proliferations leucocytaires typiques malignes' CD8 IT, gp32-331 Leu2a, T8, M236, 51.1, Sous-population de cellules T Un petit nombre de T-ALL et UCHT4, 2D2, B9.4. 1, Pour la plupart cytotoxiques/ de T-CLL B9.3. 1, B9.7.6, B9.2.4, suppressives B9.8.6, B9.11.10, B9. 1.1, C1 0, T81 1 CD9 [nT-nB, gp241 BA2, DU-ALL-1, FMC8, Monocytes La plupart des ALL A cellules SJ9A-4, WB3 ni T-ni B Un petit nombre de B-CLL CD10 [nT-nB, gplOOI J5, BA3, NL-1, 24.1, Cellules pre-B La plupart des ALL b cellules VIL-Al Polynucleaires ni T-ni B CD1 1 IM, G, ul M01, B2. 12, M522 Monocytes et granulocytes Quelques stades M4 et la plupart Quelques cellules medullaires des stades M5 des AML. Quelques CML CDw12 IM, G, ul 20.2, M67 Monocytes et granulocytes Un petit nombre de stades M4 et M5 des AML CDw13 IM, G, ul MY7, DU-HL60-4, MCS.2 Monocytes et granulocytes La plupart des stades Ml et un petit nombre de stades M4 ou M5 des AML, quelques CML CDw14 IM, ul 20.3, 5F1, MOPN 5, M02, Monocytes Un petit nombre de stades M4 et MOS1, MY4, MOS39, TM18, quelques stades M5 des AML MOP9, FMC17 CDw15 IG, u1 80H3, B13.9, MCS.1, 82H7 Granulocytes La plupart des stades M4 et FMC1 2, FMC1 3, WM37, Quelques cellules medullaires quelques stades M5 des AML, DU-HL60-1, FMC10, WM27, quelques CML WM30, Gb 120, TG8, WM38, TG1, DU-HL60-3, G2, B4.3, VIMD5, WM41, lGlO Voir Tableau 1. b Liste des anticorps faisant partie de la classe. Signification des abreviations utilisees: ALL, leucemie lymphoblastique aigue LL, lymphome A cellules lymphoblastiques CLL, leucemie lymphoide chronique CTCL, lymphome cutane A cellules T AML, leuc6mie myeloblastique aigue CML, leuc6mie my6loide chronique. d Pour preciser la frequence des cas positifs, on a utilise les expressions suivantes: "un petit nombre" pour les frequences comprises entre 10% et 39%, "quelques" pour les fr6quences comprises entre 40% et 70%, "la plupart" pour les frequences superieures a 70%.