Journal of Leukocyte Biology BioLegend: Treg, Th17, Stem Cell
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(Journal of Leukocyte Biology. 2001;70:685-690.)
© 2001 by Society for Leukocyte Biology

CD antigens 2001

David Mason*, Pascale André{dagger}, Armand Bensussan{ddagger}, Chris Buckley§, Curt Civin||, Edward Clark#, Masja de Haas**, Sanna Goyert{dagger}{dagger}, Martin Hadam{ddagger}{ddagger}, Derek Hart§§, Václav Horejsí&||||&, Stefan Meuer##, James Morrissey***, Reinhard Schwartz-Albiez{dagger}{dagger}{dagger}, Stephen Shaw{ddagger}{ddagger}{ddagger}, David Simmons§§§, Mariagrazia Uguccioni||||||, Ellen van der Schoot**, Eric Vivier{dagger} and Heddy Zola###

* Haematology Department, John Radcliffe Hospital, Oxford,
§ Division of Immunity and Infection, MRC Centre for Immune Regulation, Birmingham, and
&§§§& Celltech R&D Ltd., Great Abington, Cambridge, United Kingdom;
{dagger} Centre d’Immunologie, INSERM-CNRS de Marseille Luminy, Marseille, and
{ddagger} INSERM Institut National de la Santé et de la Recherche Medicale, Creteil, France;
|| Johns Hopkins Comprehensive Cancer Center, Baltimore, Maryland;
# Department of Microbiology, University of Washington, Seattle;
** Central Laboratory of the Netherlands, Department of Experimental Immunohematology, Amsterdam, The Netherlands;
{dagger}{dagger} Laboratory of Molecular Hematology/Division of Molecular Medicine, Cornell University Medical College, Manhasset, New York;
{ddagger}{ddagger} Kinderklinik-Medizinische Hochschule, Hannover, and
## Institut für Immunologie, Ruprecht-Karls Universität and
{dagger}{dagger}{dagger} German Cancer Research Centre, Tumor Immunology, Heidelberg, Germany;
§§ Mater Medical Research Institute, Mater Hospital, South Brisbane, and
### Child Health Research Institute, Women’s & Children’s Hospital, North Adelaide, SA, Australia;
|||| Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic;
*** University of Illinois College of Medicine, Urbana;
{ddagger}{ddagger}{ddagger} National Institute of Health, Bethesda, Maryland; and
|||||| Institute for Research in Biomedicine, Bellinzona, Switzerland

Correspondence: Prof. David Y. Mason, Haematology Department, John Radcliffe Hospital, Oxford OX3 9DU, U.K. E-mail: david.mason{at}ndcls.ox.ac.uk


    ABSTRACT
 TOP
 ABSTRACT
 THE TRADITION OF HLDA...
 THE SEVENTH HLDA WORKSHOP
 THE EIGHTH WORKSHOP
 REFERENCES
 
This paper reviews the Seventh Human Leucocyte Differentiation Antigen (HLDA7) workshop. Due to the limitations of "blind" antibody screening, which had been evident at the previous meeting in 1996, participants at HLDA7 adopted a more selective approach to the choice of antibodies by identifying new CD specificities. This resulted in the addition of more than 80 new CD specificities. Plans for the eighth and subsequent workshops are also previewed.

Key Words: HLDA workshops • leukocyte molecules


    THE TRADITION OF HLDA WORKSHOPS
 TOP
 ABSTRACT
 THE TRADITION OF HLDA...
 THE SEVENTH HLDA WORKSHOP
 THE EIGHTH WORKSHOP
 REFERENCES
 
The process of categorizing the antigenic molecules and epitopes associated with human white blood cells via the collaborative study of monoclonal antibodies dates back to the early 1980s, when the first Human Leucocyte Differentiation Antigen (HLDA) workshop was held in Paris. This initial meeting agreed on and listed only 15 of these molecular entities, but it also created a basis for an international nomenclature of leukocyte molecules (the CD scheme) and provided a forum for reporting studies on the function and practical relevance of these molecules. Six more HLDA meetings have been held since then, the most recent of which ("HLDA7") convened last year in Harrogate, United Kingdom. The published proceedings of HLDA7 will be available later this year [1 ].


    THE SEVENTH HLDA WORKSHOP
 TOP
 ABSTRACT
 THE TRADITION OF HLDA...
 THE SEVENTH HLDA WORKSHOP
 THE EIGHTH WORKSHOP
 REFERENCES
 
Aims and approaches
The Limitations of "Blind" Antibody Screening
It was apparent at HLDA6 (Kobe, Japan, 1996) that the technique of detecting molecular entities by screening coded panels of monoclonal antibodies against human cells was obsolete. Antibodies to the most immunogenic molecules had already been produced, and fewer laboratories than in the earlier days of this research were prepared to devote resources to raising new antibodies, because the probability of finding novel reagents had become increasingly less likely. As a consequence, many antibodies at the sixth workshop were reagents (submitted by laboratories that were not equipped to characterize them) that proved to be of known specificity.

Selection of Antibodies
With these considerations in mind, the seventh workshop adopted a different approach: instead of screening poorly characterized antibodies, participants selected (and actively solicited) reagents for which at least some molecular data were already available. There are a substantial number of monoclonal antibodies reactive with leukocyte-associated molecules that do not meet the traditional criterion for establishing a new CD specificity (i.e., the existence of at least two independent antibodies of the same specificity). This rule dates from the first HLDA workshop two decades ago; since then, biochemical and molecular biological techniques for characterizing the targets of new antibodies have come to be widely used. Consequently, it is now considered appropriate to establish a CD designation for a molecule if its gene has been cloned and at least one specific monoclonal antibody has been studied in the workshop.

New Workshop Sections
Four new workshop sections were introduced at HLDA7, adding to the traditional list from previous meetings; those new sections included dendritic cells, stem/progenitor cells, erythroid cells, and carbohydrate structures. Although it has been recognized for many years that monoclonal antibodies reactive with human leukocytes can be specific for carbohydrate epitopes (e.g., the carbohydrate CD category CD15 was identified at the first workshop), they had not received specific attention in any workshop before HLDA7. Although the inclusion of erythroid molecules might seem out of place in a leukocyte workshop, it was justified by the number of molecules shared between white and red blood cells (e.g., cytokine receptors) that hint at unexplored functions of red cells.

The yield of new CD specificities in the seventh HLDA workshop
The more active approach to the identification of new CD specificities represents a break with tradition, but the results have justified the new approach, because well over 80 new entities have been added to the list. This compares favorably with previous workshops (which added an average of <30 CD specificities per workshop), and, to a large extent, avoids the laborious screening in multiple laboratories of antibodies that prove to be directed against known CD molecules.

Tables 1 and 2 list the new specificities established at the seventh workshop. Full details will be found in the forthcoming proceedings publication [1 ]. Molecular, functional, and other data can be found for many of these new specificities at the "Protein Reviews on the Web" (PROW) web site (http://www.ncbi.nlm.nih.gov/prow/).


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Table 1. New CD Designations

 

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Table 2. New CD Nomenclature for ILT/LIR and KIR Molecules

 

    THE EIGHTH WORKSHOP
 TOP
 ABSTRACT
 THE TRADITION OF HLDA...
 THE SEVENTH HLDA WORKSHOP
 THE EIGHTH WORKSHOP
 REFERENCES
 
Plans for the eighth workshop are progressing well. The meeting will convene in Adelaide, Australia, in 2004 under the aegis of Prof. H. Zola (see http://www.hlda8.org). It is sometimes assumed that the catalog of surface molecules associated with human hemopoietic cells is now essentially complete, but there is abundant evidence in the literature for novel surface molecules that merit study at the next workshop and that could provide the basis for new CD designations. Table 3 comprises a list of potential new molecules reported after the production of monoclonal antibodies and also a more extensive list of surface molecules identified via gene cloning. In most instances, no antibodies are available against the putative new leukocyte/endothelial markers in this latter group. Specific and well-characterized reagents, whether monoclonal or polyclonal, are needed not only for detecting these new "virtual" molecules, but also for defining functional domains, for characterizing three-dimensional protein structure, and for analyzing protein-protein interactions. Cloning of gene sequences often reveals multiple members of new or existing molecular families (e.g., the Toll-like receptors) and might identify surface receptors that bind more than one ligand or vice versa (e.g., the TALL-1 and APRIL ligands for transmembrane activator and CAML interacting protein and BCMA). Furthermore, several leukocyte-associated markers have been cloned from mice and other species, and almost all will have human homologues. The eighth workshop will provide a forum for a range of antibody-based studies relating to this accumulating corpus of genomic and proteomic data.


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Table 3. Examples of Possible Future CD Specificities

 
As in the seventh workshop in which four new sections were added, it might be possible to include neuronal cells in the eighth workshop. Many neuronal cells express cell surface proteins found on leukocytes and vice versa (e.g., CD56, CD100, CD168, and CD171). Furthermore, the guidance cues used by neuronal cells share similarities to those involved in leukocyte extravasation, so the expression of these molecules in common might reflect shared biological processes. It might also be noted that other molecules such as the mucins, thought to be primarily associated with epithelial cells, are now being described on leukocytes.

Finally, it remains to be established how the eighth and subsequent HLDA workshops should deal with lineage- or stage-restricted leukocyte molecules that are localized within the cell cytoplasm (or nucleus). Given the importance of many of these molecules in signaling pathways initiated via known surface CD molecules, their identification and study are an inevitable extension of the work of the first seven HLDA workshops. Whether a new "intracellular CD" categorization scheme is devised for such molecules, they are of interest for many laboratories studying human hematopoietic cells, and their investigation is among the aims of the next workshop.

Received August 2, 2001; accepted August 4, 2001.


    REFERENCES
 TOP
 ABSTRACT
 THE TRADITION OF HLDA...
 THE SEVENTH HLDA WORKSHOP
 THE EIGHTH WORKSHOP
 REFERENCES
 

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