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Development
of T3/T
Cell
By
Acquisition
of mature
receptor
delineate
tion.
the
we
cascade
expression
transcription
NTRATHYMIC
step pathway
of the
receptor
(TCR),’
subunits
must
and
cell
their
multichain
munine
and
in
human
immature
of
T
mental
region
and
rearrange-
combine
with
implicate
the
T
occurs
of
early,
and
precedes
An
ontogenic
hierarchy
analogous
genes26’27
might
of TCR
fi,
a,
and
to immunoglobulin
be suspected,
but
little
-y
gene
heavy,
K,
information
cytoplasm
surface
before
expression
normal
and neoplastic
T cells.3#{176}
In addition
to the development
maturing
stage-related
thymocytes
surface
antibodies,
eg,
T6
(CD7)
markers,
of early
T cell
express
molecules,
(CD1),
rear-
are
which
I (CD2),
useful
of
for defining
Although
differentiation.3t’32
transcripts
linked
the
of
to
cell
surface.
the
develop-
antigen
recogni-
Inc.
in T cell
TCR-T3
expression
precursor
other
development
is not
apparently
are
T cells prior
T cell-associated
to T
cascade.
For
can be found
gene
surface
only after T rearrangements
the sequence
of rearrangement
early,
middle,
and
late
known,
coordinately
developmental
of 3A 1 (CD7)
the TCRG,
I, and
-y genes
a series
of human
precursor
Analysis
of pre-T
expressed
genes
rearrangemolecules
occur.33’34
and tran-
in humans,
we
T cell neoplasms
stages
of
thymocyte
neoplasms
coordinated
suggests
with
a model
development
of
mechanism.
in
in
MATERIALS
Cells.
microscopy
blastic
lymphoma
Viable
cell
as either
and
were
surface
were
classified
lymphoblastic
for cell
by conven-
leukemia
as T cell
used
performed
avidin-biotin
previously
Viable
phenotyping.
antibodies
and
analyzed
as
described.35
cell
fluorescence-activated
selected
stages
the role of these
acute
immunotyped
suspensions
METHODS
neoplasms
lineage
surface
or lymphoas described.33
marker
study
and
DNA/RNA
extraction.
T acute lymphoblastic
leukemia
cell lines,
provided by the American
Type Culture Collection
(Rockville,
MD)
included CEM, 8402, Molt-4, and Jurkat.
Sunnyvale,
3A1
AND
T lymphoblastic
tional
clonal
differentiation
with monoclonal
and
of
of the ICR
receptors,
(CD5),
TI
tran-
A
assayed
antigen
gene
complex
encoding
molecules
generally
appear
To determine
Cell
of
a series
detectable
Tl
whereas
complex.
successively
and
exists
when
molecules
representing
this regard.
Both T and T genes rearrange
early in thymic
development,’8’2’
but the ontogeny
of Ta gene
rearrangements
has not yet been
determined
because
munine
and
human
a
regions
are too large
(-35
kilobase
[kb])
for
conventional
restriction
fragment
analysis.6’28’29
With regard
to T3, immunoreactive
T3 protein
appears
to accumulate
in
the
Ta
a model
genes
(CD2),
differentiation.
These
studies
revealed
a hierarchy
of rearrangement
and expression
of TCR
genes
synchronous
with
changing
surface
marker
profiles
and expression
of the T3
Transcripts
of a third
detected
in fetal murine
thymocytes,
approximately
coincident
with the appearance
of Tfl mRNA,
but, except
for some munine
cytotoxic
T cells,
remain
for only a brief time.’7”8
rangements
1
of intracellular
on
provide
& Stratton.
with
the
cell surface
scniption
investigated
Ti
multichain
presented
of
surface
in neoplastic
of
a hierarchy
gene
expressed
example,
the
is
and
T cells.
surface
cell
Neoplasms
appearance
events.
the
here
by Grune
ment,33
investigations
receptor,
in human
(CD5)
the
late
T3,
reported
some
/3 (Ta)
As
finally,
cell
1987
cell
Ti
and
orchestration
tion
antigen
a (Ta)
T
Findings
involves
a multiand transcniprecognition.
Prior
their
the
S
protein.
and,
are
with
T cell
(CD3)
cell
molecule.
is coordinated
development,
thymocyte
of
and
variable
T cells
transcription
the
(CD7)
Independent
‘‘ ‘
of Ta gene transcription.’2’8
gene, T,’925 have been
the
gene
products
T3.
throughout
onset
rearranging
encoding
translational
which
persists
3A1
membrane
successful
protein,
events
$
surface
genes
undergo
stages
of
of T3#{244}
mRNA.
appear
Pre-T
Cossman
Jeffrey
expression
scription
T3
T cell
in Human
and
surface
to
matura-
late
of
T cell differentiation
featuring
the rearrangement
ofgenes
encoding
antigen
activation
to expression
antigen
T cell
Expression
Uppenkamp,
effort
concurrently
of the
of the
an
precursor
and
Rearrangements
by surface
ment,
middle,
appear
.‘y genes
T cell
to
human
and
preceded
Subsequent
early.
Michael
In
leading
differentiation.
$
the
thymus.
of clonal
Gene
Pittaluga,
and
the
of events
a series
receptor
tional
in
representing
intrathymic
Stefania
function
occur
analyzed
neoplasms
I
T cell
repertoire
Receptor
CA)
cells were
by indirect
sorter
(FACS
treated
with
mono-
immunofluorescence
in a
II, Becton
Dickinson,
Cytoplasmic
staining
on acetone-fixed
cytocentrifuge
complex
immunoperoxidase
of
T3
was
preparations
with
detection
technique
an
as
outlined.35
analysis.
High-molecular-weight
DNA
was cxtracted
from lymphoid
cells and digested
to completion
with the
appropriate
restriction
endonuclease
(BamHI,
EcoRI,
HindIll,
and
Bc/-I
from
Biolab,
New
England
Nuclear,
Beverly,
MA),
sizeDNA/RNA
From
the
National
Hematopathology
Cancer
Section.
Institute,
National
Laboratory
Institutes
of
Pathology,
ofHealth,
fractionated
Bethesda,
MD.
Submitted
June
Address
Institutes
30, 1 986;
reprint
of
requests
Health.
Building
October
accepted
to Dr
J.
/0,
30, 1986.
Cossman
Room
at
2N1
/0,
NCI.
National
MD
Bethesda,
20892.
The publication
charge
payment.
“advertisement”
indicate
T
/
this fact.
987 by Grune
costs
ofthis
article
This
article
must
in
accordance
defrayed
18
U.S.C.
be
in part
hereby
§1734
by page
marked
solely
to
Blots
& Stratton,
0006-497l/87/6904-0014$3.00/0
1062
with
were
therefore
Inc.
by electrophoresis
in agarose
gels,
and
transferred
to
nylon paper (Gene Screen Plus, Dupont,
New England
Nuclear).33
The blots were hybridized
with random-primed
32P-labeled
DNA
probes at specific
activities
of 300 to 600 cpm/pg.
The following
probes
were used: a subcloned
constant
region of the fi chain
(Aval-Pstl
fragment
of cDNA YT35 provided
by T. W. Mak2), a
full-length
cDNA of Ta (PYI4
provided
by T. W. Mak6), and a
genomic
fragment
including
the J, region of the human
T7 gene
(HindIIl-EcoRl
fragment
of M13H60
provided by T. Rabbitts.22’24)
were
Total
guanidinium
autoradiographed
cellular
RNA
was
isothiocyanate/CsCI2
following
high-stringency
isolated
by
washes.
ultracentrifugation
gradient.36
Twenty
Blood. Vol 69. No 4 (April), 1987:
on
micrograms
pp
1062-1067
a
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
T
CELL
RECEPTOR
IN
PRE-T
1063
NEOPLASMS
of total RNA
formaldehyde
was subjected
to electrophoresis
through
1% agarose/
denaturing
gels and was transferred
to nylon
filters.
Hybridization
was carried out with probes described
above and also
with
a human
T38 cDNA37
provided
by C. Terhorst,
Harvard
Medical School. High-stringency
washes were carried out at 50#{176}C
in
0.1 X SSC for I S minutes,
and blots were autoradiographed
by
standard
techniques.
RESULTS
All samples
Phenotyping.
markers
and expressed
Each
stron.gly
reacted
were
selectively
For example,
markers
neoplasms.
and
(1
3)
(CD1),
a
which
were
all B cell
in these
early
T cell
was negative
in 2 cases
expressed
expressed
with
T cell markers
(Table
I).
(CD7),
but other
T cell
expressed
TI I (CD2)
alternatively
marker
unreactive
one on more
with
3A1
by
(CD5);
TI
cortical
T6
thymocytes,
was
unreactive
in 5 of 10 samples
(I, 2, CEM,
8402, HSB);
surface
T3 (CD3)
was positive
in only 2 of 10 samples.
contrast,
intracellular
2, and
3)
and
cytoplasmic
T3 was detectable
displayed
a combined
distribution
DNA
(Fig
lines.
in three
Cases
I and
( I,
3 cases
membrane
and
Fig 1 .
Intracellular
T3 (cT3).
Cytocentrifuge
preparations
were
immunostained
by an avidin-.biotin
peroxidase
complex
detection
system
using Leu4 as the primary
antibody.
In this
example
Jurkat
cells display
dense.
intracytoplasmic.
perinuclear
reaction
product.
In many
cells the
nuclear
membrane
also
appears
to be stained.
(Original
magnification.
x 600;
current
magnification
x 570.)
1).
Tfi gene
of five primary
rearrangements.
demonstrated
in all but
nuclear
and
In
2 displayed
rearrangements
cases and
only
germline
were
in all cell
configurations
of the T genes when analyzed
with three different
restriction
enzymes
(BamHl,
EcoRI,
and
HindlII),
as previously
reported.33
Td gene rearrangements
involved
a single
allele
(cases
3, 5, and Jurkat)
or both alleles
(in all cell lines) and,
in one
exceptional
situation,
three
deletion
of the genmline
was confirmed
by analysis
cleases.
By cytogenetic
chromosome
7, which
analysis,
carries
thus,
the three
nongermline
quence
of rearrangements
Rearrangements
of the
and
the
cell lines,
presence
coincided
tnisomy
ments
nongermline
band
(case
4).
with all three
case
the
Td bands
This latter
restriction
4 exhibited
T locus
in each sample
tested.
of chromosome
7, showed
as it did
Case
three
restriction
of
7q3538#{176};
for T.
harbored
rearrange-
Presumably,
the
might
unusually
due
a
three
genmline
TI I -
2,
(Fig
to either
large
to three
size
3).
of the
Te genes.
Tl + ) but
or “immature”
transcribed
from
a C gene
3A1
Ti
Til
T6
cT3
sT3
(CD7)
(CD5)
(CD2)
(CD1)
(CD3)
(CD3)
-
-
Case3
+
+
-
+
-
-
A
Case4
+
-
+
+
+
-
RRR
Case5
+
+
+
+
+
+
R
CEM
+
+
+
-
+
-
RR
1.3
G
8402
+
+
+
-
+
-
AR
1.3
HSB
+
+
+
-
+
-
AR
MoIt-4
+
+
+
+
+
-
AR
Jurkat
+
+
+
+
+
+
AR
-
,
<20%
in kilobases.
of cells
stained;
cT3,
intracellular
message,
ANA
-
are given
were
able
to
of a Ta
in each
contained
(3A1 +,
only the
presumably
not combined
DNA
-
stained;
to the
a deletion
to variable
T3;
sT3,
T
T3
DNA
RNA
1’,
RNA
+
sizes
T
had
T
DNA
-
of cells
We
bands
or
of Samples
-
mANA
and
genes
an early phenotype
T gene,
showed
I .0-kb
that
+
>50%
gene,
in many
cases,
with
several
T mRNA
was detectable
cases
I and
2, which
+
.
T
nongermline
Ta
in Jurkat
Case 3, with
a rearranged
incomplete
of
Ta genome.6’28’29
+
+
Lack
unreanranged
Casel
Case2
detected;
of the
were undetected
despite
digestion
a Ta rearrangement
,
copies
7pl5.23
band in Molt-4.
mRNA
transcription.
sample
(Fig
4) except
TabI e 1 . Pheno typing
Cells
are
enzymes
be due
identify
I , Fig 2). Thus,
rearrangements
4, which
different
bands
at chromosome
Ta gene rearrangements
including
cases
1 and
and
bands
are most likely a conseof each T gene in this cell.
T gene were detected
in all cases
except
for cases I and 2 (Table
or absence
of T7 and T gene
of the T gene,
located
feature
endonutnisomy
at band
nongermline
G
-
G
-
G
G
-
G
-
G
-
1.0
G
-
R
0.7
1.3
G
-
RRR
0.7
1.0. 1.3
G
RR
0.7
-
RR
0.7
G
-
RR
0.7
1.3
G
-
AR
0.7
1.3
GD
-
AR
0.7
AR
0.7
surface
1.0,
T3;
1.3
G, germline;
A
1.3, 1.5
1.3,
1.5
A, rearranged;
D, deleted;
-
-
,
none
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
1064
PITTALUGA.
C12
C12
3
4
AND
S
I’c;
I
UPPENKAMP.
Beta
‘i
2
3
4
COSSMAN
ii,
5
a.k4
-*
1.3-
1.31.0-
.i.
1.0-
-+.
S
-...
BamHI
Alpha
EcoRl
EcoRl
2
$2
3
4
I,,,,
5
BamHl
Fig 2.
T. gene rearrangements.
Genomic
DNA was digested
with
the indicated
enzyme.
size separated
in agarose
gels. and
analyzed
on Southern
blots with the J. probe. Lanes are numbered
according
to the case number.
C represents
a germline
(unrearranged)
control,
and the germline
bands are indicated
with dashes
adjacent
to the gel. No rearrangements
were detected
in either
case 1 or 2 when
digested
with both enzymes
BamHl
or EcoRI.
Rearrangements
were
detected
in all other
cases; for example.
two rearrangements
were seen in an EcoRl
digest of case 3. and
three rearrangements
were present
in a 8amHI
digest of case 4.
Cl
‘I
1.5-
1.5-
1.3-
a’.
T3-Delta
2
3 4
5
Cl
#{149}‘#{149}.
0.7-
0.7-
Fig 4.
Northern
blot analysis
of fi. a. and T3h mRNA.
Lane
numbers
refer to the individual
case numbers.
and mRNA sizes are
given in kilobases
(kb) on left.
Transcripts
were detected
in all
samples
except
cases 1 and 2. Both the 1 .3-kb and 1 .0-kb message
sizes could
be detected
in several
cases.
T, transcripts
were
detected
in normal
thymus,
case 5. and in the Jurkat
cell line. No
transcripts
were seen in either
cases 3 or 4, and the extremely
faint band in case 2 appearing
after prolonged
exposure
is most
likely attributable
to a small percentage
of normal
T cells (-.7%)
contaminating
this sample.
T3#{244}mRNA
was found
in varying
abundancy
in most cases but was not detected
in cases 1 or 2.
sequences.4’
messages
Both mature
(1 .3 kb) and immature
(1 .0 kb)
were
simultaneously
present
in case
5 and
T,
in
Jurkat.
Ta
of these
mature
(1 .5 kb)
two
T cell
Jurkat,
BamHl
was detectable
mRNA
in each
also
was
in all
Fig 3.
Southern
blot analysis
of the Ta gene.
with
two different
restriction
enzymes.
BamHl
cases
1 and 2 showed
the same
restriction
germline
control
(C).
Despite
digestion
and HindlII.
both
fragment
as the
samples
leukemias
protein
(Fig
simultaneously
the
700
except
devoid
in case
the
were
only
base
cases
of detectable
4). Intracellular
present
5 and
incomplete
transcribed
containing
not detected
T3b transcripts
only
both
messages
neoplasms
were
T mRNA
leukemias,
in Jurkat
and,
( I .3 kb) and
(Fig
Ta transcripts,
cells
with
surface
in any samples
pairs
(bp)
1 and
2, which
in all other
T3
were
5 and
expression.
were
detected
also
the
and
and
samples.
These
tested.
in length
intracellular
T3 protein
4).
case
surface
T3 mRNA
same
T3
were
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T CELL
RECEPTOR
IN
PRE-T
NEOPLASMS
1065
DISCUSSION
T lymphoblastic
uniform
stages
leukemias
clones
considered
of differentiation;
typically
ny.3’
characterized
Together,
and
represent
thereby
serve
compartments
neoplasms
as
models
of immature
cells
has
neoplasms
intrathymic
the pheno-
of early
T cell
of T and
B cell
precursors
and
the
of lymphocyte
evaluation
understanding
thymocytes
into
functional
of precursor
tissue30’31’33’34
T
comparisons
however,
of neoplastic
cells to normal
must
take into consideration
properties
of
malignant
cells,
expression
and
potential
culture.
In the
well-characterized
phenotypic
present
cell
range
Precursor
spectrum
study,
lines
of early
T cell
cells,
T cell
aberrant
cell
cases
span
and
the
antigen
here
encompass
development
receptor
ranging
genes
were
a
in
and
was
the sequen-
tial appearance
of T cell-associated
markers.
By analyzing
each of these critical
features
in individual
precursor
T cell
clones,
we have begun
to piece together
the coordination
of
events
the T cell developmental
in
The
earliest
identifiable
“prothymocyte,”5
was
association
were
with
retained
rearrangements
2)
neither
TI
gene
Ta
rearrangements
detection
with
was
Ta genes
at this
does
of
(cases
Lack
at this
2. Further
the
lack
and
the
indication
of expression
absence
of
intracellular
lack
B cell
markers,33
genes,33
and the 3AI +,
are
have
TI
+,
and
and
most
undergone
involve
precursor
well
+,
such
one
reported
here,
for rearrangement
or
neoplasms
rearrangements.43
both
alleles
trisomy
of chromosome
of three Te and
in
one
here,
step,
only when
that suggests
rearrange
might
full-sized
regulate
for
T7 mRNA
was
based
both
genes
T
It is
mRNA
was
seen in all five cell
intracellular
T3 was
mRNA
existence
was detected,
a
of a common
coordinated
expression
is known
prior
to appear
to localization
of T3 was identified
detected.
Two sizes
on the
only
of
of
early
in cases
mRNA,
Ta
in
outer
in
I .5
represent
complete
and incomplete
were detectable
in both case 5 and
of surface
T3 in the absence
of Ta
with obligatory
production
of a
which
is noncovalently
linked
to
surface
membrane
was
observed
not
mias analyzed,
strable
by use
low abundancy
of a genomic
cDNA
will be necessary
probes
of
1.3-kb
the
T3
is consistent
heterodimer,
complex
Although
in
but,
in T cell differentiation.
were always
simultaneously
T message
5. Provocatively,
and 1 .3 kb, which
likely
messages,
respectively,4
Jurkat.
Lack of expression
transcription
complete
a-fl
analysis
rearrangements
Intracellular
Surface
expression
which Ta mRNA
was
concurrently
by this
the 1.3-kb
T
the possible
as
of
mRNA
in cases
2 are
EARLY
message
J probe.
T3
in any
might
Further
to determine
MIDDLE
TI,
to
appear.#{176}”
of the
leuke-
not be demonanalysis
with
whether
the T
surface
T3.
immunoglobulin
Tl I + phenotypes
LATE
111
16
I
Tbeta
gene
rearranged
1-beta
marker,
Tgamma
gene
mRNA
rearranged
TaIpha
13-delta
mRNA
mRNA
cT3
s13
differentiahave
Rearrangements
and,
-,
are
3A1
gene
such primitive
cells are
These
lymphoid
cells
however,
since they
germline
3A1
T cell
Ta
1 and
not found in B lineage
neoplasms.26’42
T0 rearrangement
occurs
early
in thymocyte
tion
in
thymocyte
as
Alternatively,
it could be argued
that
not committed
to T cell differentiation.
show no evidence
of B cell commitment,
of
OfTa
in cases
the cortical
genes
thymocyte
differentiation,
plasma
membrane.#{176}
I
presence
inherent
locus.6’28’29
of immaturity
of T6,
TI I
+,
transcripts
Ta
and
of rearrangement
T and T genes,
is unprecedented,
and absence
suggests
that Ta genes might
not yet be rearranged
and
T
The “mature”
in cases 4 and
that
T3
3A1
of
of nongermthe
difficulty
in the absence
1 and
enzymes,
preclude
the
rearrangements
however,
stage
restriction
not
genes
Td33 nor T. gene
transcribed.
cases
TCR
in
lack
be ascertained
reported
factor(s)
the
murine
(CD7),
whose
Neither
several
because
of gene
to the
of 3A1
I, in cells
form.
apparently
in these
rearrangement,
TI
demonstrable
digestion
line
or
analogous
expression
germline
were
despite
surface
either
in the
process.
stage,
phenotype,
and
occur as early events
that T and T genes
T and T3 genes.
receptor
expression
T and
cannot
findings
identified
finding
to cells with
rearranged
and
genes
and a nearly
mature
T
with
developments
in antigen
recombination
cells
detected.
lines and
the germline
configuration,
transcribed
antigen
receptor
cell phenotype.
Associated
gene
Whether
human
rearranged.
As a subsequent
from
retained
thymocyte
sT3-,
of an early differentiation
stage. As with T, it is in
that we see the first evidence
of T7 gene rearrange-
apparently
noteworthy
gene
during
early
cT3-,
ment.
on
development.
presented
T cell
whose
as
of phenotype
we analyzed
primary
which,
collectively,
neoplasms
of intrathymic
primitive
such
instability
Its
T6+,
+,
indicative
this cell
T cell
or cell
lines.’2’4’30’3’ Direct
cell differentiation,
the
TI
of the devel-
mature,
by analysis
either
patient
T transcripts
are incomplete,
and their
I .0-kb size
from a D-J-C
transcript
following
D-J joining.4’
Case
current
study is characterized
by transcription
of the
T mRNA
without
detectable
complete
( 1 .3 kb)
transcripts.
ontoge-
malignancies
The
been
expanded
obtained
from
stages,
results
3 in the
I .0-kb
relatively
of lymphocyte
for
development.’2’4’26’#{176}’31’3335’42
opment
are
to be arrested
at
they generally
reflect
lymphoblastic
lineage
lymphomas
exceptional
7 apparently
three T alleles.
similarly
may
case
provided
In early
Fig 5.
Hierarchy
of T3/T
cell receptor
development.
Precursor T cell neoplasms
can be roughly
segregated
into three
compartments-early.
middle.
and late. The phenotypic
expression of cells within
each compartment
is shown
along with the
chronology
of events
beginning
with
rearrangement
of T cell
receptor
genes and progressing
to their transcription
and. ultimately.
to expression
of the T3 molecular
complex.
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
PITTALUGA,
1066
gene
is transcriptionally
active
in these
human
pre-T
neo-
plasms.
The picture
that has emerged
from the current
precursor
T cell neoplasms
is a cascade
beginning
expression,
T gene
followed
rearrangement;
transcription,
and
by T I and T 1 1 expression,
T gene
transcription,
intracellular
ly, Ta transcription
and
T3
the
to speculate
is mediated
T I , and
T I I , which
cellular
factors
this
might
serve
in the
cells,
(Fig
5).
recognition
function
within
the thymus.
as receptors
thymic
it is interesting
precursor
T3
final-
of
It is
that
regulation
of antigen
receptor
by surface
molecules,
such as 3A1,
present
regard,
and,
ofsurface
antigen
events
to note
“prothymocytes,”
for humoral
mesenchyme
3A1
Analysis
The ordered
genes
of the
present
studies
investigation
of murine
We
Terhorst
into
pro-
and expression
outlined
in
is consistent
with
recently
fetal
thymocytes#{176} and
human
of
the
reported
T cell
ACKNOWLEDGMENT
In
entry
should
molecules.
leukemias.49
on
to
expresses
a moiety
of the coordination
.
hierarchy
of rearrangement
T cell receptor-T3
complex
or
appears
COSSMAN
ADDENDUM
microenvironment.
3A1
AND
of gene expression
during
T cell differentiation
vide leads into the identification
of regulatory
that
prior
and perithymic
with antibody
and Tfl and
T36 gene
accumulation;
appearance
In all, the elaboration
of the
T cells is shaped
by regulated
tempting
development
analysis
of
with 3AI
thymus,
detectable
UPPENKAMP,
the
thank
Dr T. W.
for T3 cDNA,
grateful
Mak
and
for the
and
Ta
Dr T. W. Rabbitts
to Dr J. Wang-Peng
for cytogenetic
T cDNAs,
Dr C.
for J DNA.
We are
analysis.
REFERENCES
I.
Hedrick
SM,
Cohen
DI,
Nielsen
EA,
Davis
MM:
Isolation
of
cDNA
clones encoding
T cell-specific
membrane-associated
proteins. Nature
(London)
308:149,
1984
2. Yanagi
Y, Yoshikai
Y, Leggett
K, Clark SP, Aleksander
I,
Mak TW: A human T cell-specific
cDNA clone encodes a protein
having extensive
homology
to immunoglobulin
chains. Nature (Lon308:145,
don)
1984
3. Siu G, Clark SP, Yoshikai
Y, Malissen
M, Yanagi
E, Mak TW, Hood L: The human T cell antigen receptor
by variable,
generate
4.
diversity
Sim
GK,
A, Kappler
Nature
5.
and
a complete
Yague
Arden
genes
of
structure
of human
that
rearrange
to
P. Palmer
T-cell
E, Augustin
and
receptor
and
structure
receptor.
constant
region
genes
cDNA
clones
chains
of the
Proc NatI
8.
Sci USA
A, Stobo
antigen
for human
receptor
T cell
Acad
Weiss
the T cell
specific
T cells
heterodimer
82:3430,
J: Requirement
receptor
M, Mak
and
from
TW:
of
Nature
Analysis
the alpha
a human
T-cell
1985
for the coexpression
on a malignant
human
and
ofT3
T cell
line.
of
beta
line.
and
J Exp
Med 160:1284,
1984
9. Meuer SC, Acuto 0, Hussey RE, Hodgon JC, Fitzgerald
KA,
Schlossman
SF, Reinherz
EL: Evidence
for the 13-associated
90K
heterodimer
as
the T-cell
antigen
receptor.
Nature
(London)
303:808, 1983
10. Borst J, Prendiville
MA, Terhorst
C: Complexity
of the
human
T lymphocyte-specific
cell surface
antigen
T3. J Immunol
128:1560, 1982
I I Brenner
MB, Trowbridge
IS, Strominger
JL. Cross-linking
of
human
T cell receptor
proteins:
Association
between
the T cell
.
idiotype
40:183,
#{237}3
subunit
and
the
T3
glycoprotein
heavy
subunit.
T-cell
development.
Proc
NatI
Acad
Sci
315:765,
H:
1985
HR,
Kisielow
Ontogeny
P. Kiefer
the
of
T-cell
M,
antigen
Steinmetz
receptor
M, von
the
within
Nature
(London)
313:592,
1985
17. Snodgrass
HR. Dembic
Z, Steinmetz
M, von Boehmer
H:
Expression
of T-celI antigen receptor during fetal development
in the
thymus.
Nature
(London)
315:232,
1985
18. Raulet DH, Garman
RD. Saito H, Tonegawa
S: Developmental regulation
of T-cell receptor
gene expression.
Nature
(London) 314:103, 1985
19. Saito
H, Kranz DM, Takagaki
Y, Hayday
AC, Eisen HN,
Tonegawa
5: A third rearranged
and expressed
gene in a clone of
cytotoxic
T lymphocytes.
Nature
(London)
312:36, 1984
20. Hayday
AC, Saito H, Gillies SD, Kranz
DM, Tanigawa
G,
Eisen HN, Tonegawa
5: Structure,
organization,
and somatic rearrangements
of T cell gamma
genes. Cell 40:259, 1985
21
Kranz DM, Saito H, Heller M, Takagaki
Y, Haas W, Heisen
HN, Tonegawa
5: Limited diversity of the rearranged
T-cell ‘y gene.
thymus.
a-chain.
5, Sohn U, Wilson BI, Minden
and sequences
of the variable,
joining
of the human T-cell receptor
a-chain.
Nature
(London)
316:837,
1985
7. Yanagi
Y, Chan A, Chin B, Minden
(London)
Boehmer
(London)
316:783, 1985
6. Yoshikai
Y, Clark
SP, Taylor
MD, Mak TW: Organization
in human
16. Snodgrass
Siu G, Hood LE: Diversity
of mouse T-cell antigen
JL,
expression
USA 82:4503,
1985
14. Royer HD, Ramarli
D, Acuto 0, Campen
Ti, Reinherz
EL:
Genes encoding the T-cell receptor a and fi subunits
are transcribed
in an ordered
manner
during
intrathymic
ontogeny.
Proc NatI Acad
Sci USA 82:5510, 1985
I 5. Samelson
LE, Lindsten
T, Fowlkes
Bi, van den Elsen P.
Terhorst
C, Davis MM, Schwartz
RH: Expression
of genes of the
T-cell antigen receptor complex
in precursor
thymocytes.
Nature
1984
1984
family
a
segments
J, Marrack
312:771,
B, Lotz
the
gene
Cell 37:393,
J, Nelson
J: Primary
(London)
joining
gene.
V
Y, Strauss
is encoded
gene
Cell
1985
12. Yoshikai
Y, Yanagi Y, Suciu-Foca
N, Mak TW: Presence of
T-cell receptor
mRNA
in functionally
distinct T cells and elevation
during intrathymic
differentiation.
Nature
(London)
310:506,
1984
13. Collins
MKL,
Tanigawa
G, Kissonerghis
A-M,
Ritter
M,
Price KM, Tonegawa
S, Owen Mi: Regulation
of T-cell receptor
.
Nature
22.
(London)
Lefrar.c
313:752,
1985
Rabbitts
M-P,
genes encoding
the T-cell
rearrangement
in different
TH:
Two
tandemly
‘y constant-region
T-cell
types.
organized
sequences
Nature
show
(London)
human
multiple
316:464,
I 985
Murre
23.
C,
Waldmann
Waldmann
TA,
Shows
rearranged
in leukaemic
some 7. Nature
(London)
Lefranc
24.
distinct
M-P,
T-cell
(London)
25.
Quertermous
iL,
Waldmann
Organization,
26.
U,
Hieter
PA,
Seidman
CC,
Bongiovanni
KF,
iG:
A, Rabbitts
variable-region
TH:
Rearrangement
genes
in
human
of two
DNA.
319:420,
1986
T, Murre C, Dialynas D, Duby AD, Strominger
TA, Seidman
iG: Human
T-cell ‘y chain genes:
diversity,
Korsmeyer
Morton
Human ‘y-chain genes are
T cells and map on short arm of chromo316:549,
1985
Forster
-y-chain
Nature
RA,
TB,
and
Si, Arnold
Sharrow
SO,
rearrangement.
A, Bakhshi
LeBien
TW,
Science
23 1 :252,
Kersey
1986
JV, Siebenlist
JH, Poplach
DG,
A, Ravetch
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
T
CELL
RECEPTOR
IN
PRE-T
1067
NEOPLASMS
Leder
P, Waldmann
TA: Immunoglobulin
gene rearrangement
cell surface antigen
expression
in acute lymphocytic
leukemias
cell and B cell precursor origins. i Clin Invest 71:301, 1983
27.
Hieter
PA,
immunoglobulin
A-producing
28.
Korsmeyer
29.
a-chain
Winoto
genes
T-cell
between
MP,
Stewart
surface
antigen
and
SF:
. Reinherz
NatI
EL,
thymocytes
Acad
32.
i Clin
stages
Discrete
of normal
Sci
Haynes
Si,
and
malignancies.
3 1
deleted
are
290:368,
P: Human
or rearranged
in
USA
BF,
Warnke
RA,
iS,
Levy
cells
Invest
76:248,
R:
Discordance
of the
expression
in blast
MKL,
mon
Mi:
from
maps
Leu-4
childhood
(T3)
T lympho-
1q35,
Hemler
ME,
Schroer
Blood
68:134,
iA,
Shelhamer
van den
J, Neckers
LM,
in a case
ofcommon
Arnold
Elsen
38.
Caccia
L,
Mak
N,
The
Kronenberg
M,
T
K,
of the
intrathymic
subunit
during
39:261 , I 984
A, Korsmeyer
acute
B, Borst
C: Isolation
i, Malissen
TW:
SF:
B cell origin
Si:
lymphoblastic
cell
T-cell
i:
Molecular
New
Mak
Cold
i, Coligan
iE,
a
Spring
Markham
clones encoding
the 20k
complex.
Nature
(Lon-
ofcDNA
receptor
M,
receptor
Saxe
D,
H, Yoshikai
fi
chain
Haars
R,
Bruns
Y, Simon
genes
are
GAP,
M,
located
Hood
on
gene
Croce
CM:
T
in
receptor
cells.
at band
Science
228:580,
cell acute
T-cell
receptor
lines
gene
and
lymphoblas-
of neoplastic
stages
YT35
and
M, Mak
in human
functional
T-cell
normal
DNA
clones.
TW:
from
Nature
MD, Toyonaga
Somatic
T-cell
B, Ha K, Yanagi
rearrangement
malignancies.
ofT-cell
Proc
NatI
Y, Chin
antigen
Acad
B, Gelfand
receptor
Sci USA
gene
82:1224,
1985
45. Flug F, Pelicci
PG. Bonetti
F, Knowles
DM II, Dalla-Favera
R: T-cell receptor
gene rearrangements
as markers
of lineage and
clonality
in T-cell neoplasms.
Proc NatI Acad Sci USA 82:3460,
I985
46. Rabbitts
TH, Stinson A, Forster A, Foroni L, Luzzatto
L,
Catovsky
D, Hammarstrom
L, Smith
CIE,
Jones
D, Karpas
A,
Minowada
J, Taylor AMR: Heterogeneity
of T-cell beta-chain
gene
in
human
leukemias
and
lymphomas.
EMBO
i
1985
DF, Hensley LL, Ho W, Haynes BF: Human T cell
during the early stages of fetal thymic maturation.i Immunol 135:1752, 1985
48. Haars R, Kronenberg
M, Gallatin
WM,
Weissman
IL, Owen
FL, Hood
L: Rearrangement
and expression
of T cell antigen
receptor and y genes during thymic development.
i Exp Med I 64: 1,
antigen
Lobach
expression
I 986
49.
Furley
Ai,
Mizutani
5, Weilbaecher
K, Dhaliwal
HS,
Ford
Toyonaga
B, Mak TW, van den
Elsen
P. Gold D, Terhorst
C, Greaves
MF: Developmentally
regulated rearrangement
and expression
of genes encoding
the T cell
receptor-T3
complex.
Cell 46:75,
1986
AM,
Willard
TW:
in human
4:2217,
Cloning,
York,
chain
31 1:385, 1984
rearrangements
Induction
leukemia.
NK, Solo-
PC,
T-cell
of non-T
for discrete
of T-cell
Minden
44.
E,
47.
P. Shepley
5, Terhorst
Ramachandran
Ti
1982
T3 glycoprotein
of human
don) 312:413, 1984
Goverman
Nowell
of human
to rearrangements
A model
leukemia
(London)
1986
36. Maniatis
T, Fritsch
EF, Sambrook
Laboratory
Manual.
Cold Spring
Harbor,
Harbor Laboratory,
1983
Orkin
beta
thymic
N EngI J Med 307:1251,
37.
J, Schlossman
leukemia.
Rearrangements
1980
DL,
Royer HD, Acuto 0, Fabbi M, Tizard R,
iE, Reinherz
EL: Genes
encoding
the
antigen/M
HC receptor
undergo rearrangement
ontogeny
prior to surface T3-Ti expression.
Cell
AF,
prone
subunit
Spurr
37:1091,
1984
BS,
J, Emanuel
fi
for
i 3:2347,
Mi,
receptor
77:1588,
34.
Smart
Cossman
Erikson
Dunne
antigen
pre-B cell differentiation.
i Clin Invest 74:332, 1984
43. Toyonaga
B, Yanagi
Y, Suciu-Foca
N, Minden
Eisenbarth
GS, Strominger
iL, Thomas
CA, Mostowski
HS,
AS: Characterization
of a monoclonal
antibody
that defines
an immunoregulatory
T cell subset for immunoglobulin
synthesis
in
humans.
Proc NatI Acad Sci USA 77:2914,
1980
33. Pittaluga
5, Raffeld M, Lipford EH, Cossman
i: 3A1 (CD7)
expression
precedes T gene rearrangements
in precursor
T (lympho-
35.
7. EMBO
of gene
a region
PN,
T-cell
Cell
41. Born W, Yague i, Palmer
E, Kappler
i, Marrack
P: Rearrangement
of T-cell
receptor
fl-chain genes during
T-cell
development. Proc NatI Acad Sci USA 82:2925,
1985
42. Nadler
LM, Korsmeyer
Si, Anderson
KC, Boyd AW,
Slaughenhaupt
B, Park E, Jensen i, Coral F, Mayer
Ri, Sallan SE,
tic
Fauci
ofdifferentiation
Goodfellow
7 in humans.
Kung PC, Goldstein
G, Levey RH, Schlossman
of human intrathymic
differentiation:
Analysis
and leukemic
lymphoblasts
of T lineage.
Proc
Mann
neoplasms.
M,
chromosome
1985
Ritz
1985
Isobe
and
A human
to chromosome
Location
JH,
blastic)
E, Owen
40.
G, Helig
6 in mice
I984
39. Collins
1981
Tanigawa
cytoplasmic
in thymocytes
blastic
Leder
1985
Link
30.
M,
mouse
TA,
chromosome
Folsom V.
organization
and diversity
of T-cell
(London)
316:828,
1985
Hood L: Genomic
organization
of the
receptor
a-chain.
Nature
(London)
Di,
5: Unusual
genes. Nature
A, Shelley
encoding
316:832,
Diamond
AC,
H, Tonegawa
receptor
Waldmann
K light-chain
genes
B cells. Nature
(London)
Hayday
Saito
Si,
and
of T
Chan
LC,
Molgaard
HV,
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
1987 69: 1062-1067
Development of T3/T cell receptor gene expression in human pre-T
neoplasms
S Pittaluga, M Uppenkamp and J Cossman
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