From bloodjournal.hematologylibrary.org by guest on December 30, 2011. For personal use only.
2002 99: 3877-3880
doi:10.1182/blood.V99.10.3877
CD antigens 2002
David Mason, Pascale André, Armand Bensussan, Chris Buckley, Curt Civin, Edward Clark, Masja de
Haas, Sanna Goyert, Martin Hadam, Derek Hart, Václav Horejsi?, Stefan Meuer, James Morrissey,
Reinhard Schwartz-Albiez, Stephen Shaw, David Simmons, Mariagrazia Uguccioni, Ellen van der Schoot,
Eric Vivier and Heddy Zola
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BLOOD, 15 MAY 2002 䡠 VOLUME 99, NUMBER 10
CORRESPONDENCE
fied peripheral blood CD34(⫹) progenitor cells from HLA-mismatched parental
donors in children. Bone Marrow Transplant. 2001; 27:777-783.
References
1.
2.
Zaucha JM, Gooley T, Bensinger WI, et al. CD34 cell dose in granulocyte
colony-stimulating factor-mobilized peripheral blood mononuclear cell grafts
affects engraftment kinetics and development of extensive chronic graftversus-host disease after human leukocyte antigen-identical sibling transplantation. Blood. 2001; 98:3221-3227.
Handgretinger R, Klingebiel T, Lang P, et al. Megadose transplantation of puri-
3877
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Storb R, Prentice RL, Sullivan KM, et al. Predictive factors in chronic graftversus-host disease in patients with aplastic anemia treated by marrow transplantation from HLA-identical siblings. Ann Intern Med. 1983; 98:461-466.
4.
Lang P, Handgretinger R, Schumm M, et al. Transplantation of purified peripheral CD34⫹ stem cells from unrelated donors in children: effective prevention
of GvHD [abstract]. Blood. 1999;94(suppl 1):667a.
To the editor:
CD antigens 2002
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 (Human Leucocyte Differentiation Antigen) Workshop was
held in Paris. This initial meeting listed only 15 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, United Kingdom, and the proceedings of the meeting
(Leucocyte Typing VII1) have recently been published.
The aims and approaches of HLDA7. 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
obsolescent. 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 sixth workshop were
reagents (submitted by laboratories that were not equipped to
characterize them) that proved to be of known specificity.
With these considerations in mind, HLDA7 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 leukocyte-associated molecules exist that do not meet the traditional criterion for establishing a new CD specificity (ie, the existence of at least 2 independent
antibodies of the same specificity). This rule dates from the first
HLDA workshop 2 decades ago; since that time 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.
Four new sections were introduced in HLDA7 to add to the
traditional list from past meetings: 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 (eg, the carbohydrate CD category CD15
was identified at the first HLDA workshop), they had not received
specific attention at 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
Table 1. New CD designations
Designation
Section
Locus link
CD15u
Sulphated CD15
Name
Carbohydrate structures
NA
CD60a
GD3
Carbohydrate structures
NA
CD60b
9-O-acetyl-GD3
Carbohydrate structures
NA
CD60c
7-O-acetyl-GD3
Carbohydrate structures
NA
CD75
Lactosamines
Carbohydrate structures
NA
CD75s
Alpha-2,6-sialylated
Carbohydrate structures
NA
lactosamines (formerly
CDw75 and CDw76)
CD85
ILT/LIR family (see Table 2)
Dendritic cells
NA
CD110
MPL, TPO R
Platelets
4352
CD111
PRR1/Nectin1
Myeloid cells
5818
CD112
PRR2
Myeloid cells
5819
CD133
AC133
Stem/progenitor cells
8842
CD156b
TACE/ADAM17
Adhesion structures
6868
CD158
KIR family (see Table 2)
NK cells
NA
CD159a
NKG2A
NK cells
3821
CD160
BY55
T cells
CD162R
PEN5
NK cells
CD167a
Discoidin domain R
Adhesion structures
11126
6404
780
(DDR1)
CD168
RHAMM
Adhesion structures
3161
CD169
Sialoadhesin
Adhesion structures
6614
CD170
Siglec-5
Adhesion structures
8778
CD171
L1
Adhesion structures
3897
CD172a
SIRP alpha
Adhesion structures
8194
CD173
Blood group H type 2
Carbohydrate structures
NA
CD174
Lewis y
Carbohydrate structures
NA
CD175
Tn
Carbohydrate structures
NA
CD175s
Sialyl-Tn
Carbohydrate structures
NA
CD176
TF
Carbohydrate structures
NA
CD177
NB1
Myeloid cells
NA
CD178
Fas ligand
Cytokine/chemokine
356
receptors
CD179a
Vpre-B
B cells
7441
CD179b
Lambda 5
B cells
3543
CD180
RP105
B cells
4064
CD183
CXCR3
Cytokine/chemokine
2833
receptors
CD184
CXCR4
Cytokine/chemokine
7852
receptors
CD195
CCR5
Cytokine/chemokine
1234
receptors
CDw197
CCR7
Cytokine/chemokine
1236
receptors
CD200
OX2
Nonlineage molecules
CD201
EPC R
Endothelial cells
4345
CD202b
Tie2 (Tek)
Endothelial cells
7010
CD203c
NPP3/PDNP3
Myeloid cells
5169
CD204
Macrophage scavenger R
Myeloid cells
4481
10544
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3878
BLOOD, 15 MAY 2002 䡠 VOLUME 99, NUMBER 10
CORRESPONDENCE
Table 1. New CD designations (continued)
CD220
Insulin R
Nonlineage molecules
3643
CD221
IGF1 R
Nonlineage molecules
3480
CD222
Mannose-6-phosphate/IGF2 R
Nonlineage molecules
3482
CD223
LAG-3
Nonlineage molecules
3902
CD224
Gamma-glutamyl transferase
Nonlineage molecules
2678
CD225
Leu13
Nonlineage molecules
8519
CD226
DNAM-1 (PTA1)
T cells
CD227
MUC.1
Nonlineage molecules
4582
CD228
Melanotransferrin
Nonlineage molecules
4241
CD229
Ly9
Nonlineage molecules
4063
CD230
Prion protein
Nonlineage molecules
5621
CD231
TALLA-1/A15
Nonlineage molecules
7102
CD232
VESP R
Nonlineage molecules
10154
CD233
Band 3
Erythroid cells
6521
CD234
Fy-glycoprotein (DARC)
Erythroid cells
2532
CD235a
Glycophorin A
Erythroid cells
2993
CD235b
Glycophorin B
Erythroid cells
2994
CD235ab
Glycophorin A/B
Erythroid cells
NA
functional, and other data can be found for many of these new
specificities on the PROW site.2
The eighth workshop. Plans are well advanced for the eighth
workshop, to be organized in Adelaide, Australia, in 2004 under the
aegis of Professor H. Zola (see http://www.hlda8.org). It is
sometimes assumed that the catalogue 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 HLDA8, and that could
provide the basis for new CD designations. Table 3 comprises both
a list of potential new molecules reported following the production
of monoclonal antibodies and also a longer list of surface molecules identified via gene cloning, for which in most instances, no
antibodies are available. 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 3-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 (eg, the Toll-like
receptors) and may identify surface receptors that bind more than
one ligand or vice versa (eg, 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. HLDA8 will provide a forum for
a range of antibody-based studies relating to this accumulating
corpus of genomic and proteomic data. As in HLDA7, in which 4
new sections were added, it may be possible to include new cell
types in HLDA8. For example, many neuronal cells express
surface proteins found on leukocytes and vice versa (eg, CD56,
CD100, CD168, CD171). Furthermore, the guidance cues used by
neuronal cells share similarities to those involved in leukocyte
Table 2. New CD nomenclature for ILT/LIR and KIR molecules
Designation
Name
Section
Locus link
CD205
DEC205
Dendritic cells
4065
CD206
Macrophage mannose R
Dendritic cells
4360
CD207
Langerin
Dendritic cells
50489
CD208
DC-LAMP
Dendritic cells
NA
CD209
DC-SIGN
Dendritic cells
30385
CDw210
IL-10 R
Cytokine/chemokine
3587; 3588
receptors
CD212
IL-12 R
Cytokine/chemokine
3594
receptors
CD213a1
IL-13 R alpha 1
Cytokine/chemokine
3597
receptors
CD213a2
IL-13 R alpha 2
Cytokine/chemokine
3598
receptors
CDw217
IL-17 R
Cytokine/chemokine
23765
receptors
10666
crossreactive mabs
CD236
Glycophorin C/D
Erythroid cells
NA
CD236R
Glycophorin C
Erythroid cells
2995
CD238
Kell
Erythroid cells
3792
CD239
B-CAM
Erythroid cells
4059
CD240CE
Rh30CE
Erythroid cells
6006
CD240D
Rh30D
Erythroid cells
6007
CD240DCE Rh30D/CE crossreactive
Erythroid cells
NA
mabs
CD241
RhAg
Erythroid cells
6005
CD242
ICAM-4
Erythroid cells
3386
CD243
MDR-1
Stem/progenitor cells
CD244
2B4
NK cells
CD245
p220/240
T cells
CD246
Anaplastic lymphoma kinase
T cells
CD247
Zeta chain
T cells
NA
51744
NA
238
919
Designation
Name
The ILT/LIR family
CD85a
ILT5/LIR3
CD85b
ILT8
CD85c
LIR8
CD85d
ILT4/LIR2, MIR10
CD85e
ILT6/LIR4
CD85f
ILT11
CD85g
ILT7
CD85h
ILT1/LIR7
CD85i
LIR6
CD85j
ILT2/LIR1, MIR7
CD85k
ILT3/LIR5
CD85l
ILT9
CD85m
ILT10
The KIR family
between white and red cells (eg, cytokine receptors) that hint at
unexplored functions of red cells.
The yield of new CD specificities in HLDA7. 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 fewer than 30 CD specificities per workshop),
and it also largely avoided the laborious screening in multiple
laboratories of antibodies that often prove to be directed against
known CD molecules.
Tables 1 and 2 list the new specificities established at HLDA7.
Full details can be found in Leucocyte Typing VII,1 and molecular,
CD158z
KIR3DL7/KIRC1
CD158b1 and CD158b2
KIR2DL2/p58.2 and KIR2DL3/p58.3
CD158a
KIR2DL1/p58.1
CD158c
KIR2DS6/KIRX
CD158d
KIR2DL4
CD158e1 and CD158e2
KIR3DL1/p70 and KIR3DS1/p70
CD158f
KIR2DL5
CD158g
KIR2DS5
CD158h
KIR2DS1/p50.1
CD158i
KIR2DS4/p50.3
CD158j
KIR2DS2/p50.2
CD158k
KIR3DL2/p140
For further details of this classification, based on the position of the genes on
chromosome 19q;13.4 from centromeric to telomeric loci, see André et al.3
From bloodjournal.hematologylibrary.org by guest on December 30, 2011. For personal use only.
BLOOD, 15 MAY 2002 䡠 VOLUME 99, NUMBER 10
CORRESPONDENCE
3879
Table 3. Examples of possible future CD specificities
Molecule
Molecule size
Cell types
Comments
Reference(s)
Identified following antibody production
AM-3K antigen
70 & 120 kd
Macrophages
BDCA-2, BDCA-3, & BDCA-4 antigens
ND
Dendritic cells
Identifies subsets of dendritic cells
—
5
4
BENE
17 kd
Endothelium
“Raft-associated” member of MAL family;
6
interacts with caveolin-1
CMRF-44
ND
Dendritic cells
Differentiation/activation marker
7, 8
CMRF-56
95 kd
Dendritic cells
Differentiation/activation marker
7, 8
H47 antigen
100 kd* (120 kd)
T cells & most NK cells, B cells, and
Involved in T cell activation?
9
New lymphoma marker?
10
monocytes
Hal-1
200 kd* (100 kd)
T cells, EBV-transformed B-cells,
myelomonocytic cells, anaplastic large
cell lymphoma
LAK1 antigen
120 kd
LGL and LAK cells
—
11
LAK2 antigen
110 ⫹ 140 kd
LGL and LAK cells
—
11
NKp80
80 kd dimer
NK cells and CD56-positive T cells
Novel member of the killer cell lectinlike
12, 13
receptor gene family, encoded by
KLRF1 gene; triggers NK cell
cytotoxicity
VAP-1†
90 kd
Endothelium
Mediates lymphocyte-endothelial
14, 15
adhesion; has monoamine oxidase
activity
Wue-1 antigen
94 kd
Plasma cells
Stimulates growth of plasma cells
16
184 aa
B cells
TNFR family member; receptor for
17, 18
Identified via gene cloning
BCMA‡
TALL-1 and APRIL
B7-H2
302 aa
Dendritic cells
New member of B7 family; binds ICOS on
19
activated T cells
CLEC-1
280 aa
Dendritic cells
Novel C-type lectin-like receptor with
20
cytoplasmic tyrosine-based motif
CMRF-35A
224 aa
NK cells, neutrophils, monocytes,
dendritic cells and subset of T
lymphocytes
CMRF-35H
300 aa
NK cells, neutrophils, monocytes,
dendritic cells and subset of T
lymphocytes
CS1
ND
NK cells
Novel Ig superfamily receptors; CMRF-
21, 22
35H contains 3 cytoplasmic tyrosine
based motifs
Novel Ig superfamily receptors; CMRF-
21, 22
35H contains 3 cytoplasmic tyrosine
based motifs
Novel receptor belonging to CD2 subset
23
of Ig superfamily
DC-STAMP
470 aa
Dendritic cells
Novel protein containing 7 putative
24
transmembrane domains
EMR3
652 aa
Mainly leucocyte restricted. Highest levels
on neutrophils, monocytes and
Novel EGF-TM7 molecule; interacts with
25
a surface ligand on myeloid cells
macrophages
Flt-1 (VEGFR-1)
ND
Endothelial cells, monocytes
GPRv53
390 aa
Leukocytes
G-protein-coupled histamine receptor
—
27
26
IRTA1, IRTA2
ND
Subpopulations of B cells
Homologous to the Fc and inhibitory
28
receptor families
M160
1453 aa
Macrophages
New member of scavenger receptor
29
cysteine-rich superfamily
MARCO§
520 aa
Macrophages
Class A scavenger receptor; involved in
30, 31
bacterial clearance in vivo
TACI
293 aa
B cells
TNFR family member; receptor for
32
TALL-1 and APRIL
TREM-1㛳
ND
Neutrophils and subset of monocytes
Novel Ig superfamily receptor; triggers
33, 34
neutrophil secretion (eg, IL-8) and
degranulation; associates with DAP12
TREM-2㛳
ND
Neutrophils and subset of macrophages
Novel Ig superfamily receptor; activates
macrophages; associates with DAP12
ND indicates not determined.
*The nonreduced size; reduced size given in parentheses.
†Vascular adhesion protein.
‡B cell maturation factor.
§Macrophage receptor with collagenous structure.
㛳Triggering receptor expressed on myeloid cells.
33, 34
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3880
CORRESPONDENCE
extravasation, and 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 eighth and
subsequent HLDA workshops should deal with lineage- or stagerestricted 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 studying
human hematopoietic cells, and their investigation will be among
the aims of the next workshop.
David Mason, Pascale André, Armand Bensussan, Chris Buckley,
Curt Civin, Edward Clark, Masja de Haas, Sanna Goyert, Martin Hadam,
Derek Hart, Václav Hořejšı́, Stefan Meuer, James Morrissey,
Reinhard Schwartz-Albiez, Stephen Shaw, David Simmons,
Mariagrazia Uguccioni, Ellen van der Schoot, Eric Vivier, and Heddy Zola
Correspondence: David Y. Mason, LRF Immunodiagnostics Unit, John
Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom; e-mail:
[email protected]
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