From the Departments of Microbiology and Immunology,
¶ Pathology and Comprehensive Cancer Center,
Cellular and
Molecular Biology, ** Biology, and
Surgery,
University of Michigan Medical School, Ann Arbor, Michigan 48109
Received for publication, February 9, 2001, and in revised form, March 9, 2001
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ABSTRACT |
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The MHC class II transactivator (CIITA) is a
critical transcription factor that regulates genes involved in antigen
presentation function. At least three functional forms of CIITA
gene products are transcribed from three different promoters. The CIITA
gene expressed in dendritic cells (DC-CIITA) has a unique first exon encoding an extended N-terminal region of CIITA. Here, we show that the
N terminus of DC-CIITA has high homology to a caspase recruitment
domain (CARD) found in components of apoptosis and nuclear factor- The MHC1 class II
transactivator (CIITA) was initially identified as a critical
transcription factor that is required for both constitutive and
interferon- Four different isoforms of human CIITA transcripts have been identified
(11). Each isoform is transcribed from a separate promoter that confers
expression specificity. Thus, the first exon of each isoform is unique,
but the rest of the exons are shared by all isoforms. Forms I and III
are constitutively expressed primarily in dendritic cells (DCs) and B
cells, respectively (11). The interferon- Studies using B-CIITA have demonstrated that CIITA contains four
domains shared by all isoforms: the acidic domain,
proline/serine/threonine-rich domain, the GTP binding domain, and the
domain with leucine-rich repeats (1). Each domain serves a unique
function, and all domains are required for proper transactivation of
the MHC class II gene (12-17).
The caspase recruitment domain (CARD) was first identified as a peptide
module present in the prodomains of upstream caspases and adapter
molecules such as CED-4/Apaf-1 and RAIDD that mediates the recruitment
of caspases via homophilic CARD-CARD interactions (18). More recently,
the CARDs have been found in other molecules including Nod1 and RICK
that are components of NF- Nod1, a cytosolic protein with homology to plant disease-resistant R
gene products and Apaf-1, shares a strikingly similar domain
organization with CIITA (19) (Fig. 1D). Both Nod1 and CIITA
have N-terminal effector domains, a centrally located nucleotide binding domain, and leucine-rich repeats at the C terminus. The effector domain of Nod1 is the CARD that is not present in the CIITA
expressed in B cells. Here, we report that the first exon of DC-CIITA
encodes a CARD. We found that DC-CIITA containing the CARD is a more
potent transactivator for MHC class II expression than B-CIITA and that
the CARD is required for enhanced transactivation activity. Unlike
other CARD-containing proteins, however, DC-CIITA does not seem to
interact with members of the caspase family or regulate apoptosis.
These findings provide the first evidence for a novel regulatory role
for the CARD in transcription. The unique feature of the DC form of
CIITA may explain the enhanced expression level of MHC class II in DCs.
Plasmid Constructs--
To clone the first exon of the dendritic
cell form of CIITA, PCR was performed using human genomic DNA and the
primers 5'-EcoRI-FLAG-DC (5'-CTGGAATTCATGGACTACAAAGACGATGACGATAAAATGAACAACTTCCAGGCCATCCTG-3') and the 3' fourth exon (5'-GTCCTTGCTCAGGCCCTC-3'). To facilitate the
cloning and detection by Western blot, an EcoRI site and a FLAG epitope tag were introduced within the 5' primer. The PCR product
was digested with EcoRI and SacI, followed by
ligation with a fragment encompassing the second through the last exon of full-length B-CIITA (1). The expression vector for CARD itself was
produced by inserting the EcoRI and SacI fragment
of the PCR product into the pCDNA3 expression vector.
Full-length L27Q DC-CIITA and CARD(L27Q) were generated by overlapping
PCR using two sets of primers: 5'-EcoRI-FLAG-DC and 3'-L27Q
(5'-GTGCAGGCCCTCCAGGACAACCTGCTG-3') and 5'-L27Q
(5'-CAGCAGGTTGTCCTGGAGGGCCTGCAC-3') and 3' fourth exon. Secondary PCR
was carried out using the primary PCR products as a template. The PCR
product was digested with EcoRI and SacI and
cloned into the pCDNA3 expression vector to generate CARD(L27Q),
and full-length L27Q was generated by replacing the corresponding
fragment of wild-type DC-CIITA with this fragment. The integrity of the
mutants was confirmed by sequencing.
The MHC class II promoter-driven luciferase construct contains 2 kilobases of the E Cell Culture--
The human kidney cell line 293T was maintained
in Click's medium with 10% fetal bovine serum, 100 units/ml
penicillin, 100 µg/ml streptomycin, 2 mM
L-glutamine, and 10 Transfection and Luciferase Assays--
The transfection of 293T
cells was performed using the calcium phosphate method. For the
activation of the MHC class II promoter, 1 × 105
cells were plated in 12-well plates. Each well of cells was transfected with 100 ng of the E
For the Western blots, 2 × 105 293T cells were plated
in 6-well plates and transfected with the CIITA expression vector as indicated in the figure legends.
Reverse Transcription PCR--
Reverse transcription PCR was
performed as described (8). The CIITA-specific primers used
were: the first exon of DC-CIITA, 5'-TGCTGAAGGAGGACCTCCTCT-3'; B-CIITA,
5'-TGATGAGGCTGTGTGCTTCTG-3'; the second common exon,
5'-GAAGGTGGCTACCTGGAGCTT-3'; and the fourth common exon,
5'-GTCCTTGCTCAGGCCCTC-3'. The Flow Cytometric Analysis--
Cells were suspended in cold 1×
phosphate-buffered saline supplemented with 1% fetal bovine serum.
Staining was performed in the same buffer. L243 antibody was used to
examine MHC class II. Flow cytometry was performed using FACScan.
Western Blot--
Nuclear and cytoplasmic fractionation (21) and
Western blots were performed as described without any modification (9). An anti-CIITA antibody was used to detect endogenous CIITA (22).
Sequence Alignment--
CARD homology in DC-CIITA was predicted
and confirmed by two independent methods: ISREC ProfileScan, maintained
by the Swiss Institute for Experimental Cancer Research, and PSI-BLAST,
maintained by the National Center for Biotechnology Information.
The First Exon of the CIITA Gene Expressed in DCs Encodes a
CARD--
Because the difference among the three isoforms of CIITA
lies in the N termini (11), we studied the first exon unique to CIITA
that is expressed in DCs in detail. We first compared CIITA transcripts
from Raji B lymphoblastoid cells with DCs prepared from human
peripheral blood. To distinguish the different isoforms of CIITA
transcripts, we used the 5' primer specific for the first exon unique
to DC- or B-CIITA transcripts (Fig.
1A). The 5' primer recognizing
the second exon was used to detect the common exon. The 3' primer from
the fourth exon was used for all reactions. Consistent with the
previous report (11), transcripts containing the B cell-specific first
exon were present in both B and DCs (Fig. 1B). However, the
DC-specific first exon was detected in dendritic cells, not in B
cells.
To further characterize the N-terminal 94-amino acid region that is
unique to DC-CIITA, we searched the public databases to identify
peptides with homology to this region. The search revealed that the
peptide encoded by the first exon of DC-CIITA has significant homology
to CARDs found in members of the caspase family, as well as those found
in caspase activators and NF- DC-CIITA Activates the MHC Class II but Not the NF- DC-CIITA Is a More Potent Activator than B-CIITA--
We then
compared the transactivation activities of DC-CIITA and B-CIITA using
the E
We wanted to examine the transactivation ability of the two isoforms in
more detail. To do this, an increasing amount of each CIITA expression
vector was co-transfected with a constant amount of the E
Because the above data were generated using transient assays, we tested
whether DC-CIITA is also more potent in activating the endogenous MHC
class II gene. We stably transfected DC-CIITA or B-CIITA to RJ2.2.5
cells and compared the levels of CIITA proteins and MHC class II on the
cell surface. When the same amounts of cellular protein from two
independent clones of B-CIITA- or DC-CIITA-transfected cells were
analyzed, DC-CIITA proteins were barely detectable (Fig.
4A). Despite a lower level of
DC-CIITA protein, the levels of MHC class II on the cell surface were
comparable between DC-CIITA- and B-CIITA-expressing cells (Fig.
4B).
We next examined the levels of endogenous CIITA proteins in primary DCs
that express higher levels of surface MHC class II than B
cells.2 To do this, we prepared total cell lysates from
Raji and human DCs and compared endogenous CIITA proteins by
immunoblotting with the anti-CIITA antibody. Consistent with the data
from transfection studies (Fig. 3C), the levels of DC-CIITA
protein were lower than those of B-CIITA (Fig. 4C). Taken
together, the results indicate that the transactivation potential of
DC-CIITA is greater than that of B-CIITA.
The CARD of DC-CIITA Confers Higher Transactivation
Activity--
We reasoned that the higher potential of DC-CIITA as a
transactivator might be caused by the presence of the CARD. The
conserved leucine residue at position 27 in the CARD of RAIDD is
critical because mutation of this residue resulted in a loss of
function (25). Similarly, the corresponding mutation of the CARD of
Nod1 abolished its ability to interact with RICK or activate NF-
We transfected the mutant and compared its transactivation potential to
that of wild-type DC-CIITA and B-CIITA. As shown in Fig.
5A, the luciferase activity of
the cells transfected with the L27Q mutant was equivalent to that of
B-CIITA, suggesting that the additional activity of DC-CIITA is caused
by the CARD. The level of L27Q protein was equivalent to that of the
wild-type DC-CIITA (Fig. 5A).
The CARD is known to interact with other CARD-containing proteins
through homophilic CARD-CARD association (18, 23, 26-29). If the CARD
is responsible for a higher transactivation potential of DC-CIITA, then
the CARD by itself might inhibit DC-CIITA function by interfering with
the interaction of the CARD of CIITA with the CARD of a partner. To
test this, we generated a construct expressing the wild-type CARD
itself or the point mutant of the CARD with the L27Q amino acid
substitution. We co-expressed wild-type or mutant CARD in 293T cells
with DC-CIITA or B-CIITA in the presence of the E
The CARD is a critical domain mediating protein-protein interactions
and is known to be present in proteins in the cell death and the
NF-
The mechanism by which the CARD serves as a transcriptional regulator
of CIITA is not clear. We ruled out the possibility that the higher
transactivation activity of DC-CIITA can be attributed to more
efficient nuclear translocation and/or increased accumulation in the
nucleus (Fig. 3D). Because one amino acid substitution at a
conserved residue known to be critical for CARD-CARD interaction abolishes the CARD activity, the CARD of CIITA may act by recruiting a
protein. Interactions between CARDs have been shown to be selective (19, 23). For example, the CARD of Apaf-1 interacts with caspase-9 CARD, whereas the CARD of Nod1 binds preferentially to RICK CARD (19,
23, 29). Therefore, it is likely that CIITA CARD recognizes a CARD of
an unidentified protein(s), possibly a transcription factor(s), or a
protein that cooperates with the DC-CIITA complex to enhance
transactivation of the MHC class II gene. It would be of a great
interest to identify the partner molecule for DC-CIITA.
The conservation of the domain organization and the sequence homology
between DC-CIITA and Nod1 suggest that these proteins may have
originated from a common ancestral protein. Nod1 has been shown to
confer responsiveness to bacterial lipopolysaccharides (30), indicating
that Nod1 may have been evolved to become a sensor of pathogens.
DC-CIITA, on the other hand, might be adapted as a transcription factor
to induce MHC class II expression, which initiates the cascade of T
cell-mediated immune responses resulting in elimination of pathogens.
Thus, both DC-CIITA and Nod1 may have been evolved from an ancestral
protein that might have been involved in host defenses against pathogens.
DCs are considered the most efficient antigen-presenting cells. They
take up pathogens and antigens efficiently, express high levels of MHC
class II, migrate from the sites of antigen acquisition to secondary
lymphoid organs, and stimulate T cells (31). Our data suggest that the
presence of the CARD is at least partly responsible for the enhanced
level of MHC class II expression in DCs. However, we cannot rule out
the possibility that DC-CIITA performs other functions specific for
DCs. The assessment of the role of CARD in vivo would
clarify the role of DC-CIITA and provide an insight toward a better
understanding of differences between CIITA isoforms.
B
signaling pathways. However, DC-CIITA does not regulate cell death, nor
does it induce nuclear factor-
B activity. Instead, DC-CIITA is
transcriptionally a more potent activator of the MHC class II gene than
the form expressed in B cells. A single amino acid substitution in the
CARD of DC-CIITA, predicted to disrupt CARD-CARD interactions,
diminished the transactivation potential of DC-CIITA. These
results indicate that the CARD in the context of CIITA serves as a
regulatory domain for transcriptional activity and may function to
selectively enhance MHC class II gene expression in dendritic cells.
INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS AND DISCUSSION
REFERENCES
-inducible expression of MHC class II genes (1-3). CIITA
also activates other genes involved in antigen presentation such as the
invariant chain and the HLA-DM genes (4, 5). The
significance of CIITA function in vivo was further confirmed
by the generation of CIITA
/
mice that display a
phenotype similar to patients with severe combined immunodeficiency
disease, the bare lymphocyte syndrome (6, 7). CIITA also acts as a
negative regulator for genes expressed in CD4 T cells including the
interleukin-4 and FasL genes (8-10). Therefore, CIITA has
dual functions, acting as an activator or a repressor depending on the
target promoter.
-inducible form of CIITA
(Form IV) is transcribed by the last promoter (11). The second isoform
is poorly characterized, and the specificity of its expression is
unknown. The B cell form of CIITA (B-CIITA) has been extensively
studied for transactivation function (12), but the function of the form
unique to dendritic cells (DC-CIITA) remains unknown.
B signaling pathways (19). The association
of the CARD of Nod1 with the corresponding CARD of RICK induces the
dimerization of RICK, which in turn activates NF-
B (19). Thus, the
CARD functions as an effector domain that mediates specific homophilic
interactions with downstream molecules to activate diverse signaling events.
MATERIALS AND METHODS
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ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS AND DISCUSSION
REFERENCES
promoter (BglI-BalI)
(E
-luciferase), and the cytomegalovirus promoter-driven
-galactosidase and wild-type B cell isoform of CIITA were as
described (8, 9). Full-length Nod1, the CARD of Nod1, and the NF-
B
promoter-driven luciferase (NF-
B-luciferase) have been described
(19).
5 M
2-mercaptoethanol. Cells were grown at 37 °C with 5%
CO2. RJ2.2.5 cells were maintained in RPMI 1640 medium
containing the same supplements as for the 293T cells. Human dendritic
cells were prepared as described (20).
-luciferase, 100 ng of the CIITA expression vector, and 100 ng of
-galactosidase expression vector. To assess the activation of the NF-
B promoter, 0.3 ng of NF-
B-luciferase was transfected with 33 ng of Nod1 or DC-CIITA expression vector in the
presence of 33 ng of
-galactosidase (19). Two days
post-transfection, cells were harvested, washed with 1×
phosphate-buffered saline, and lysed in Reporter lysis buffer (Promega,
Madison, WI) followed by luciferase and
-galactosidase assays as
described (9).
-galactosidase readings were used to normalize the
relative luciferase activity of each sample for all transfections.
RJ2.2.5 cells were transiently transfected using 5 × 106 RJ2.2.5 cells, 10 µg of the E
-luciferase, 5 µg
of
-galactosidase expression vector, and 20 µg of the CIITA
expression vector by electroporation. To generate stable transfectants
of RJ2.2.5, cells were electroporated with 20 µg of B-CIITA or
DC-CIITA and were then selected with 1 mg/ml G418.
-actin-specific primers were as
described (6).
RESULTS AND DISCUSSION
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS AND DISCUSSION
REFERENCES
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Fig. 1.
Characterization of the CIITA isoform
expressed in DCs. A, the exon organization of the CIITA
gene. The numbers in boxes indicate exons, and the
arrows show the positions of the primers used for reverse
transcription PCR in B. The diagram was not drawn to scale.
Exons beyond the fourth one are not shown. B, DC-CIITA is
expressed in DCs. The primer located at the first exon of DC or B cell
type shown in A was used in conjunction with the primer at
the fourth exon to detect the transcripts. The 5' PCR primer used to
detect the common exons is located at the second exon as illustrated in
A. The dilution factors shown for the actin transcripts
refer to first strand templates used for PCR reactions. C,
sequence comparison of CIITA CARD with CARDs of members of the caspase
family. Alignment of CARDs with the following GenBankTM/EBI
accession numbers is shown. Human (h) and mouse
(m) dendritic cell-type CIITA (AF000002 and AF100709), Nod1
(AF113925), RICK (AF027706), ARC (AF043244), RAIDD (U79115), caspase-2
(U13021), Ced-3 (L29052), Ced-4 (X69016), caspase-9 (U56390), Apaf-1
(AF013263), and c-IAP-1 (L49431) is shown. The residues identical and
similar to those of Nod1 are shown by reverse and dark
highlighting, respectively. The putative helices, H1a to H6, are
shown based on the three-dimensional structure of the CARD of Apaf-1
(23). D, comparison of the domain organization of DC-CIITA
and Nod1. A, acidic; P/S/T,
proline/serine/threonine rich; NBD, nucleotide binding
domain; LRR, leucine-rich repeats.
B signaling molecules such as Nod1 and
RICK (Fig. 1C). The predicted CARD of DC-CIITA has a total
of six
helices (shaded boxes) that are a hallmark of
CARDs (23). Furthermore, the residues most conserved among the CARDs of
various molecules are also conserved in DC-CIITA. Of particular
interest, the CARD of Nod1 has the highest homology with CIITA CARD
(25% identity, 43% similarity; Fig. 1D). Both DC-CIITA and
Nod1 have the CARD at the N terminus, the nucleotide binding domain in
the middle, and the leucine-rich repeat at the C terminus. Thus,
DC-CIITA and Nod1 share similar domain organization.
B
Promoter--
Nod1 promotes caspase-9-induced apoptosis and induces
NF-
B activity (19). Because of the high homology between DC-CIITA and Nod1, we asked whether DC-CIITA acts as a regulator of apoptosis and/or NF-
B activation. To test this, we co-transfected 293T cells
with the expression vector for DC-CIITA or Nod1 along with the
NF-
B-luciferase reporter construct. The cytomegalovirus
promoter-driven
-galactosidase was co-transfected to monitor
transfection efficiency. As a control, we tested the activation of the
MHC class II promoter. As expected, Nod1 activated the NF-
B but not
the MHC class II promoter (Fig. 2).
Conversely, DC-CIITA did not activate NF-
B but did activate the MHC
class II promoter. In addition, the expression of DC-CIITA did not
induce apoptosis when overexpressed in 293T cells.2 DC-CIITA but not Nod1
also activated the MHC class II promoter in RJ2.2.5 B cells that have a
defect in the endogenous CIITA gene (24) (see below).2
These data suggest that the activities of DC-CIITA and Nod1 are distinct and that DC-CIITA does not participate in NF-
B
activation.
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Fig. 2.
CIITA activates the MHC class II but not the
NF- B promoter. The luciferase reporter
driven by either the NF-
B or the MHC class II E
promoter was
co-transfected with the expression vector encoding Nod1 or DC-CIITA.
The fold induction was calculated using the luciferase value from cells
transfected with the reporter gene and the empty expression vector as
1. The error bar for the DC-CIITA is too small to be visible.
-luciferase reporter. When DC-CIITA was co-transfected into
293T cells, the luciferase activity was greater than that from cells
transfected with B-CIITA (Fig.
3A, left panel). DC-CIITA also showed a higher activity in RJ2.2.5 cells, indicating that DC-CIITA is a more potent activator than B-CIITA (Fig.
3A, right panel).
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Fig. 3.
DC-CIITA is a more potent activator for the
MHC class II promoter. A, DC-CIITA or B-CIITA was
co-transfected with the E -luciferase reporter to 293T cells
(left panel) or RJ2.2.5 cells (right panel). The
-fold induction was calculated the same way as described in the legend
to Fig. 2. The results shown are from three independent experiments.
B, dose-dependent activation of the MHC class II
promoter by different isoforms of CIITA. 1.5 µg of E
-luciferase
reporter and 0.5 µg of cytomegalovirus-
-galactosidase were
co-transfected with the indicated amount of the CIITA expression
vector. The error bar for B-CIITA is too small to be shown.
C, the same cell lysate used in B was used for
the Western blot using the anti-CIITA antibody to determine the level
of CIITA protein. 25 µg of cell lysate was loaded. D,
nuclear (N) and cytoplasmic (C) fractions were
prepared from 293T cells that were transfected with DC- or B-CIITA. 10 (B-CIITA) and 30 µg (DC-CIITA) of protein were loaded.
-luciferase
reporter. As shown in Fig. 3B, the induction of the MHC
class II promoter by DC-CIITA was greater than by B-CIITA at any given
concentration of DNA. However, this was not caused by more DC-CIITA
protein being expressed in cells because DC-CIITA was expressed at a
lower level than B-CIITA upon transfection (Fig. 3C). We
next tested whether the protein levels of DC-CIITA in the nucleus are
greater than those of B-CIITA, which may result in higher
transactivation. When nuclear fractions of the two forms of CIITA were
compared, the level of DC-CIITA was much lower than B-CIITA (Fig.
3D). In addition, the relative distribution of DC-CIITA between the two compartments was comparable with that of B-CIITA.
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Fig. 4.
MHC class II expression of cells stably
transfected with B- or DC-CIITA. A, total cell lysate
was prepared from RJ2.2.5 cells that were stably transfected with B- or
DC-CIITA. 25 µg of cell lysate was loaded on the SDS-polyacrylamide
gel followed by Western blot using the anti-CIITA antibody.
#1 and #2 indicate independent clones of
transfectants. B, the level of MHC class II of the same
transfectants used in A was measured by flow cytometry.
C, DCs express a lower level of CIITA proteins. Indicated
amounts of total cell lysate prepared from Raji (lane 1 and
2), RJ2.2.5 (lane 3), and hDCs (lane
4-6) were used for the SDS-polyacrylamide gel. The anti-CIITA
antibody was used to detect CIITA protein.
B (19). Therefore, we generated a mutant of DC-CIITA by substituting the
conserved leucine with glutamine at position 27 (L27Q) to determine
whether a functional CARD in DC-CIITA is required for enhanced
transcriptional activity.
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Fig. 5.
The presence of the CARD confers the higher
transactivation activity of CIITA. The E -luciferase construct
was co-transfected with the expression vector for the wild-type
DC- CIITA, L27Q, or B-CIITA to 293T (left panel) and
RJ2.2.5 cells (right panel). The DNA amount used for the
transfection was described under "Materials and Methods." 25 µg
of total cell lysate from cells transfected with the wild-type
(WT) or L27Q was used for the Western blot shown in the
inset of the left panel. The anti-CIITA antibody
was used for the blot. B, the CARD itself can inhibit
DC-CIITA transactivation function. 293T cells were transfected with 1.5 µg of E
-luciferase, 15 ng of the CIITA expression vector, and 1.5 µg of CARD or CARD(L27Q). *, p < 0.001 versus control (n = 5).
-luciferase
reporter. The wild-type, but not CARD(L27Q), reduced the
transactivation potential of DC-CIITA (Fig. 5C, lanes 1-3). The inhibition was specific for DC-CIITA because
wild-type CARD did not affect the ability of B-CIITA to transactivate
the MHC class II promoter (Fig. 5C, lanes
4-6).
B activation pathway. Here, we demonstrated for the first time
that the CARD participates in transcriptional regulation in the context
of DC-CIITA. DC-CIITA is a unique transcription factor possessing a
CARD. CIITA CARD did not interact with several CARD-containing proteins
tested so far, including caspase-1, -2, -4, -9, c-IAP-1, RICK, Nod1,
Nod2, ARC, Bcl-10, CARD-12, and ICEBERG.2 In addition,
neither cell death2 nor NF-
B activation seemed to be
affected by DC-CIITA (Fig. 2). Rather, the CARD in the context of CIITA
confers a higher activity for CIITA as a transcription factor to
activate the MHC class II genes but not the molecules involved in cell death.
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ACKNOWLEDGEMENTS |
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We thank Dr. Laurie Glimcher for providing the anti-CIITA antibody. We are also very grateful to Dr. Wes Dunnick for thoughtful discussions and critical reading of the manuscript.
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FOOTNOTES |
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* This work was supported by National Institutes of Health Grant AI41510 (to C. -H. C.), National Institutes of Health Immunology Training Grant T32-AI07413 (to T. S.), National Institutes of Health National Research Service Award 5-T32-GM07544 from the National Institutes of General Medicine Sciences (to K. N.), and the National Institutes of Health Medical Scientist Training Program Student Training Grant T32-GM07863 (to C. S. K. Y.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
§ These authors contributed equally to this work.
§§ To whom correspondence should be addressed: Dept. of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109. Tel.: 734-647-7666; Fax: 734-764-3562; E-mail: heechang@umich.edu.
Published, JBC Papers in Press, March 13, 2001, DOI 10.1074/jbc.M101295200
2 K. Nickerson, T. J. Sisk, N. Inohara, G. Núñez, and C.-H. Chang, unpublished data.
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ABBREVIATIONS |
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The abbreviations used are:
MHC, major
histocompatibility complex;
CIITA, class II transactivator;
DC, dendritic cell;
B-CIITA, B cell form of CIITA;
DC-CIITA, dendritic
cell-specific CIITA;
CARD, caspase recruitment domain;
PCR, polymerase
chain reaction;
NF-B, nuclear factor-
B.
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REFERENCES |
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