(Journal of Leukocyte Biology. 2001;70:685-690.)
© 2001
by Society for Leukocyte Biology
CD antigens 2001
David Mason*,
Pascale André
,
Armand Bensussan
,
Chris Buckley
,
Curt Civin||,
Edward Clark#,
Masja de Haas**,
Sanna Goyert
,
Martin Hadam
,
Derek Hart
,
Václav Horej
í&||||&,
Stefan Meuer##,
James Morrissey***,
Reinhard Schwartz-Albiez

,
Stephen Shaw

,
David Simmons

,
Mariagrazia Uguccioni||||||,
Ellen van der Schoot**,
Eric Vivier
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;
Centre dImmunologie, INSERM-CNRS de Marseille Luminy, Marseille, and
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;

Laboratory of Molecular Hematology/Division of Molecular Medicine, Cornell University Medical College, Manhasset, New York;

Kinderklinik-Medizinische Hochschule, Hannover, and
## Institut für Immunologie, Ruprecht-Karls Universität and


German Cancer Research Centre, Tumor Immunology, Heidelberg, Germany;

Mater Medical Research Institute, Mater Hospital, South Brisbane, and
### Child Health Research Institute, Womens & Childrens 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;


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
|
|---|
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
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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
|
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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/).
 |
THE EIGHTH WORKSHOP
|
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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.
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.
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