The Journal of Immunology, 2002, 168: 2083-2086.
Copyright © 2002 by The American Association of Immunologists
Reference: CD Antigens 20021
David Mason2,
Pascale André,
Armand Bensussan,
Chris Buckley,
Curt Civin,
Edward Clark,
Masja de Haas,
Sanna Goyert,
Martin Hadam,
Derek Hart,
Václav Ho
ej
í,
Stefan Meuer,
James Morrissey,
Reinhard Schwartz-Albiez,
Stephen Shaw,
David Simmons,
Mariagrazia Uguccioni,
Ellen van der Schoot,
Eric Vivier and
Heddy Zola
 |
Introduction
|
|---|
The
Proceedings of the 7th Human Leukocyte Differentiation Antigen (HLDA)
Workshop are about to be published, detailing more than 80 new CD
specificities. The next Workshop, planned for 2004, will continue this
process, and a number of candidate CD molecules in the literature,
identified by antibody production or gene cloning, are listed in this
update.
|
The tradition of HLDA Workshops
|
|---|
The process of categorizing the antigenic molecules and epitopes
associated with human white cells, via the collaborative study of
monoclonal antibodies, dates back to the early 1980s, when the first
HLDA Workshop was held in Paris, France. This initial meeting listed
only fifteen agreed molecular entities, but it created an
internationally agreed basis for the nomenclature of leukocyte
molecules (the CD scheme), and also provided a forum for reporting
studies on their function and practical relevance. A further six HLDA
meetings have been held since the first Paris meeting. The most recent
of these ("HLDA7") took place in 2000 in Harrogate, U.K., and the
proceedings of the meeting will be published this year (Leucocyte
Typing VII, Oxford University Press).
|
The aims and approaches of the 7th HLDA Workshop
|
|---|
The limitations of "blind" antibody screening
It was apparent at the previous meeting, HLDA6, held in Kobe,
Japan, in 1996, that the technique of detecting molecular entities by
screening coded panels of monoclonal antibodies against human cells was
becoming obsolete. Antibodies to the most immunogenic molecules had
already been produced, and fewer laboratories than in the early days
were prepared to devote resources to raising new antibodies, since the
probability of finding novel reagents becomes ever less likely. In
consequence, many antibodies in the 6th Workshop were reagents
(submitted by laboratories that were not equipped to characterize them)
which proved to be of known specificity.
Selection of antibodies
With these considerations in mind the 7th Workshop adopted a
different approach; instead of screening poorly characterized
antibodies, reagents were selected (and actively solicited) for which
at least some molecular data were already available. A substantial
number of monoclonal antibodies reactive with leucocyte-associated
molecules exist 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 that time, biochemical
and molecular biological techniques for characterizing the
targets of new antibodies have come to be widely used. In consequence,
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 sections were introduced in the 7th HLDA Workshop to add
to the traditional list from past meetings: namely 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. The inclusion of erythroid molecules,
although it may seem out of place in a "Leukocyte Workshop," was
justified by the number of molecules shared between white and red cells
(e.g., cytokine receptors) that hint at unexplored functions of red
cells.
|
The yield of new CD specificities in the 7th HLDA Workshop
|
|---|
This more active approach to the identification of new CD
specificities represented a break with tradition, but the results
justified the new approach, since a total of well over 80 new entities
were added to the list of CD specificities. This compares favorably
with previous Workshops (an average of less than 30 CD specificities
per Workshop), and it also largely avoided the laborious screening in
multiple laboratories of antibodies that prove to be directed against
known CD molecules.
Tables I
and II list the new
specificities established at the 7th
Workshop. Full details will be found in
Leucocyte Typing VII, and molecular, functional, and other
data can be found for many of these new specificities on the Protein
Reviews on the Web (PROW) Web site
(http://www.ncbi.nlm.nih.gov/prow/).
|
The 8th Workshop
|
|---|
Plans are well advanced for the 8th
Workshop (see www.hlda8.org), to be organized in Adelaide,
Australia, in 2004 under the aegis of Prof. H. Zola (Child Health
Research Institute, Adelaide, Australia). 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 would merit
study at the next Workshop, and that could provide the basis for new CD
designations. Table III comprises a list
of potential new molecules reported following 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. It may be added that cloning of
gene sequences often reveals multiple members of new or existing
molecular families (e.g., the Toll-like receptors) and may identify
surface receptors that bind more than one ligand or vice versa, (e.g.,
the TALL-1 and APRIL ligands for TACI and BCMA). Furthermore, a number
of leukocyte-associated markers have been cloned from mice
and other species, and almost all will have human homologues. The 8th
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 7th Workshop in which four new sections were added,
it may be possible to include neuronal cells in the 8th 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 sharesimilarities to those
involved in leukocyte extravasation so the expression of these
molecules in common may reflect shared biological processes. It may
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 8th 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 is an inevitable extension of the work of the first seven HLDA
Workshops. Whether or not a new "intracellular CD" categorization
scheme is devised for such molecules, they are of interest for many
laboratories interested in human hematopoietic cells, and their study
will be among the aims of the next Workshop.
|
Footnotes
|
|---|
1 By permission of Oxford University Press. 
2 Address correspondence and reprint requests to Prof. David Y. Mason, Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, U.K. E-mail address: david.mason{at}ndcls.ox.ac.uk
Received for publication June 27, 2001.
Accepted for publication January 10, 2002.
|
References
|
|---|
-
André, P., R. Biassoni, M. Colonna, D. Cosman, L. L. Lanier, E. O. Long, M. Lopez-Botet, A. Moretta, L. Moretta, P. Parham, et al 2001. New nomenclature for MHC receptors. Nat. Immunol. 2:661.[Medline]
This article has been cited by other articles:
|
|
|
|
 
A. Woolfson, J. Stebbing, B. D. M. Tom, K. J. Stoner, W. R. Gilks, D. P. Kreil, S. P. Mulligan, L. Belov, J. S. Chrisp, W. Errington, et al.
Conservation of unique cell-surface CD antigen mosaics in HIV-1-infected individuals
Blood,
August 1, 2005;
106(3):
1003 - 1007.
[Abstract]
[Full Text]
[PDF]
|
|
|
Top
Introduction
The tradition of HLDA...