Vol.1, No.1, 8-14 (2011) Open Journal of Immunology
Copyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/OJI/
Auto-presentation of Staphylococcal enterotoxin A by
mouse CD4+ T cells
Auto-presentation by CD4+ T cells
Reuven Rasooly*, Paula M. Do, Bradley J. Hernlem
Western Regional Research Center, Agricultural Research Service, U.S. Department of Agriculture, Albany, USA; *Corresponding
Author: reuven.rasooly@ars.usda.gov
Received 27 May 2011, revised 12 June 2011, accepted 20 June 2011.
The currently accepted model for superantigen
(SAg) induced T cell activation suggests that
SAg, without being processed, cross link both
MHC class II, from Antigen Presenting Cells
(APC), and V-
, from T-cell receptor (TCR), initi-
ating nonspecific T-cell activation. This T-cell
proliferation induces a massive cy tokine release
associated with several human diseases. It is
thought that mu rine CD4 + T cells do not express
MHC class-II molecules. However, we discov-
ered that a subtype of mouse naïve CD4+ T cells
expresses MHC class II on their cell surface and
that these CD4+ T cells can perform the role of
both APC and T cells, able to present Staphy-
lococcal enterotoxin A (SEA) to itself or neigh-
boring CD4+ T cells via MHC class II, thus in-
ducing massive CD4+ T cell proliferation. Treat-
ment with neutralizing anti MHC class II anti-
body inhibits this CD4+ T cell proliferation re-
sponse. The fact that murine CD4+ T cells ex-
press MHC cl ass II offe rs new insight about S Ag
activity. Based on our findings, we propose re-
vising and extending previous models for SAg
induced T cell activation, altering previous mo-
dels of MHC class II restriction of T cell re-
sponses to SEA as well as the requirement for
SAg processing.
Keywords: MHC Class II; T-Cell; Enterotoxin
Staphylococcus aureus is a major bacterial pathogen
causing several diseases including food-borne illnesses
[1]. S. aureus produces a grou p of 21 (known) staphylo-
coccal enterotoxins (SEs) that have two separate bio-
logical activities: they cause gastroenteritis in the gas-
trointestinal tract and act as a superantigen (SAg) caus-
ing massive activation and proliferation of T-cells and
cytokine release [1]. Several studies have shown that
there is a relation between emetic and superantigenic
activities [2,3]. SAg plays an important role in patho-
genesis by undermining the specificity of the adaptive
immune response. They are reported to be associated
with etiology of several human diseases including toxic
shock syndrome, Kawasaki disease, guttate psoriasis,
eczema, rheumatoid arthritis and scarlet fever [4].
The current model for superantigen activity suggests
that native, unprocessed SAg bind directly to the -
helical chain of the MHC class II, outside the peptide
binding groove of the antigen presenting cell (APC) [5].
This binding takes place without proteolytic degradation
and fragmentation, internalization, and re-expression of
the SAg degraded short fragments on the cell surface.
This native SAg is recognized and interacts with a large
number of T-cells, which all share particular sequences
within the variable region of the chain (V-
) of the T
cell receptor (TCR), thereby stimulating ~20% of the
naïve T-cell population [6]. This trimolecular interaction
triggers massive proliferation of the T-cells subsets and
production of large quantity of cytokines that can have
pathological effects. The currently accepted model,
therefore, suggests that both types of cells; APC and T
cells, are needed for SAg induced T-cell proliferation
The currently acceptable view is that murine T-cells
do not express MHC class-II molecules [9-13], and that
professional APCs expressing MHC class II are required
for SAg induced T cell proliferation [7]. However, the
present study demonstrates for the first time that mouse
naïve CD4+ T cells
TCR express MHC class II on
their cell surface. Our data suggest that these T cells act
as APCs, capture staphylococcal enterotoxin A (SEA),
and present the SEA-MHC class II complex to itself or
R. Rasooly et al. / Open Journal of Immunology 1 (2011) 8-14
Copyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/OJI/
neighboring CD4+ T cells targeting their own surface
molecules. These events then cause proliferation. When
anti MHC class II antibodies are added to purified dou-
ble positiv e CD4+ T cells, they block T-cell auto presen-
tation and inhibit T cell proliferation.
2.1. Chemicals and Reagents
SEA was obtained from Toxin Technology (Sarasota,
FL). Bromodeoxyuridine (5-bromo-2-deoxyuridine, BrdU)
was obtained from Calbiochem (San Diego, CA). Phy-
tohemagglutinin (PHA) was obtained from Sigma Al-
drich (St Louis, MO). Anti-CD3 epsilon chain labeled
(PE), anti-
TCR labeled pacific blue, anti-CD4 anti-
body labeled with APC an ti-MHC class II an tib od y I-Ek,
anti MHC class II antibody against the subregion en-
coded glycoproteins I-Ab, I-Ad, I-Aq, I-Ed, I-Ek. And
anti-MHC class II antibody labeled with FITC or APC
were obtained fro m eBioscience (San Diego, CA). An ti-
3 T-cell receptor was obtained from BD Pharmingen
(Franklin Lakes, NJ). Imunomagnetic beads conjugated
with antibodies directed against CD3 and CD28 were
obtained from Invitrogen (Carlsbad, CA), as well as
CD4+ T-cell positive and negative isolation kits.
2.2. Splenocyte Isolation
Spleens from C57BL/6 female mice were aseptically
removed and disrupted using a syringe and needle in
Russ-10 cell culture medium (made by combining 450
ml of RPMI 1640 medium without glutamine (Gibco,
Carlsbad, CA), 50 ml Fetal bovine serum (Hyclone,
Logan, UT), 5 ml 200 mM glutamine (Gibco), 5 ml anti-
biotic-antimycotic (Gibco; containing penicillin, strep-
tomycin, and fungizone), 5 ml nonessential amino acid
mix (Gibco), 5 ml sodium pyruvate (Gibco), and 0.25 ml
of 100 mM beta mercaptoethanol (Sigma)). Cells were
centrifuged at 200 × g at 4˚C for 10 min. Red blood cells
were then lysed by adding 5 mL of red cell lysis buffer
(0.15 M NH4Cl, 10 mM KHCO3, 0.1 mM Na2EDTA).
Cells were again centrifuged and resuspended in Russ-10
medium, and viable cells were counted using trypan blue
and a hemocytometer.
2.3. Positive or Negative Isolation of Murine
CD4+ T Cells
Murine CD4 + T cells were isolated using either a posi-
tive (Dynabeads Mouse CD4 L3T4) or negative selec-
tion kit (Dynal Mouse CD4 Negative Isolation Kit), ac-
cording to the manufacturer’s instructions. Briefly, for
positive isolation, splenocytes were resuspended in iso-
lation buffer (PBS supplemented with 0.1% BSA and 2
mM EDTA) at a concentration of 1 × 107/mL, and in-
cubated with washed Dynabeads (25 l of Dynabeads
per 107 cells) for 20 mins on ice with gentle rotation.
After incubation the cells and Dynabeads were placed on
a magnet for 2 mins. The supernatant was removed and
the bead-bound cells wer e washed with isolation bu ffer 3
times. The bead-bound cells were resuspended in Russ-
10 media (107 cells per 100 l of media) and DE-
TACHaBEAD mouse CD4 was added (10 l per 107
cells) and incubated for 45 mins with gentle rotation at
room temperature. The detached cells were washed 3
times and resuspended in media. For negative isolation
of CD4 cells heat inactivated FBS and antibody were
added to splenocytes and incubated for 20 mins on ice.
The cells were washed with isolation buffer, and
pre-washed mouse depletion dynabeads were added and
incubated for 15 mins with gentle rotation at room tem-
perature. The cells and dynabeads were placed on a
magnet and the supernatant was obtained and washed.
The supernatant contained the negatively isolated mouse
CD4 T cells.
2.4. Superantigen Induced Naive T-Cell
Proliferation Assay
Cells were placed in 96-well plates (1 × 106/mL, 0.2
mL) in Russ-10 medium and treated with various con-
centrations of SEA ranging from 0.5 to 200 ng/ml fol-
lowing incubation at 37˚C in a 5% CO2 incubator. After
incubation for 48 h, cell proliferation was measured by
adding Bromodeoxyuridine (5-bromo-2-deoxyuridine,
BrdU), which was incorporated into the DNA of divid-
ing cells, 4 h before fixation as described by manufac-
turer instructions (Calbiochem, San Diego, CA). Spec-
troscopic measurements were made at an optical density
of 620 nm and 45 0 nm.
2.5. Flow Cytometry
One and a half million cells were placed through a
strainer and labeled with prospective antibodies for 40
mins. Cells were washed twice in 200 L of PBS and
resuspended in 0.5 mL of PBS. Flow cytometry and cell
sorting were performed using a FACS Vantage SE (Bec-
ton Dickinson) fitted with a Cobolt CalypsoTM 100 mW
491 nm laser (Cobolt AB, Sweden) and a cube 40 mW
640 nm laser (Coherent, Auburn, CA). The fluorescence
of FITC and PE labels were quantifed by excitation at
491 nm using 530/30 and 585/42 bandpass filters, re-
spectively. Fluorescence of APC was quantified by exci-
tation at 640 nm using a 676/29 bandpass filter (Sem-
rock, Rochester, NY).
2.6. Expansion of Cell Sorted Cells
After sorting cells were stimulated with immunomag-
netic beads coated with anti-CD3/28 in Russ-10 con-
R. Rasooly et al. / Open Journal of Immunology 1 (2011) 8-14
Copyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/OJI/
taining IL- 2 (30 U/mL).
2.7. Statistical Analysis
Statistical analysis was performed using SigmaStat 3.5
for Windows (Systat Software, San Jose, CA). Multiple
comparisons were made of PHA or with increasing con-
centrations of SEA that induce splenocytes or purified T
cell proliferation. The experiments were repeated at least
three times, and results with p < 0.05 were considered
statistically significant.
3.1. The Effect of APC-CD4+ T Cells Ratio on
Superantigen Induced Naive T-Cell
In order to activate CD4+ T-cells, a 10 to 1 ratio of
APCs to T cells is needed [14]. Our hypothesis is that
the ratio between APC and T cell is important for effi-
cient T-cell proliferation, and that there would be a re-
duction in CD4+ T-Cell proliferation response after al-
tering this ratio, because reduction in APCs limits the
number of CD4+ T cells that can bind to the SEA-APC
complex. To test this hypothesis, we increased CD4+ T
cell concentration by utilizing two types of CD4+ T cell
isolation methods; negative selection which increases the
concentration of CD4+ T cell from 22% in the average
spleen to 90%, or positive selection with an average pu-
rity of 95%. The isolated CD4+ T cells from a single
spleen preparation were cultured with three concentra-
tions of the superantigen SEA 0.5, 1 and 200 ng/ml.
Proliferation was measured on day 1 by BrdU incorpora-
tion. As shown in Figure 1, SEA induced proliferat i o n in
a dose dependent manner in all three cell cultures. Sur-
prisingly, the highly enriched positive isolated CD4+ T,
which presumably has the lowest concentration of APC
cell, provided the highest signal with highest signal-
to-noise ratio. These experiments raise the questions
whether depleting APC paradoxically increases prolife-
ration, and how complete elimination of APCs will ef-
fect proliferation.
3.2. The Superantigen Staphylococcal
Enterotoxin A Induces Proliferation
of CD4+ T Cells in the Absence of APC
To determine how elimination of APCs affects SEA
induced T cell proliferation, CD4+ T cells were purified
from splenocytes by positive and negative selection. In
these experiments, SEA was used at a concentration of
200 ng/ml. To determine the absence of APC, APC-de-
pendent mitogen PHA was used at concentration of 10
g/ml. Antibody against MHC class II was used to block
the interaction between MHC class II and the variable
region of the TCR. As shown in Figure 2, the APC-de-
splenocyteCD4 (pos)CD4 (neg)
OD 450 nm
0 ng/ml
0.5 ng/ml
1 ng/ml
200 ng/ml
Figure 1. SEA activation of purified CD4+ T-cells. Splenocytes,
positively selected, and negatively selected CD4+ T-cells were
incubated with increasing concentrations of SEA. After incu-
bation for 1 day newly synthesized DNA was measured. Error
bars represent standard errors and n = 3.
Figure 2. SEA induces proliferation of double purified CD4+ T
cells Splenocytes, positive selected and double positive se-
lected CD4+ T cells were incubated with SEA in the presence
or absence of antibody against MHC class II subregion glyco-
proteins I-Ab, I-Ad, I-Aq, I-Ed, I-Ek or I-Ek alone. After incuba-
tion for 2 days, newly synthesized DNA was measured. Error
bars represent standard errors and n = 3.
R. Rasooly et al. / Open Journal of Immunology 1 (2011) 8-14
Copyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/OJI/
pendent mitogen, PHA has high proliferative effect on
splenocytes, which contain large number of APCs. The
data also show a low effect on CD4+ T cells with posi-
tive isolation, and no proliferative effect on positive and
negative selection of CD4+ T cells. These observations
suggest that the double positive purified CD4+ T cells
lack APCs. This result is novel and interesting because
SEA was able to induce proliferation of purified CD4+ T
cells in the absence of MHC-class II expressed on APC.
However, anti MHC class II antibody against the subre-
gion encoded glycoproteins I-Ab, I-Ad, I-Aq, I-Ed and
I-Ek, but not I-Ek alone, blocked proliferation of the
doubled purified murine CD4+ T cells. This shows that
the SEA induced proliferation response is MHC class II
dependent. These observations suggest the presence of
MHC class II despite the lack of APCs.
3.3. Naïve CD4+ T Cells Can Express MHC
Class II
The presence of MHC class II in purified naïve CD4+
T cells without APC raises the question of the source of
the MHC class II molecules. Our hypothesis was that
Presort analysis of naïve splenocyte cells
(a) (b) (c) (d)
Post sort analysis of naïve splenocyte cells
(e) (f) (g) (h)
Figure 3. Naïve CD4+ T cells can express MHC class II Mouse splenocyte were immunostained with anti CD4, anti CD3, anti 
TCR and anti MHC class II antibody were simultaneously analyzed by flow cytometry in a single analysis. The data prior to sorting
show that 2.6% of the gated splenocytes are positive for all 4 antibodies (A-D). Cell sorting enrichment increased concentration of T
cells expressing MHC class II (E-H). (I) fluorescent microscopy of CD4+ T-cells, anti-CD4 antibody (is labeled with APC (red) and
anti-MHC class II is labeled with FITC (green). The data suggest that these are indeed CD4+ T cells expressing MHC class II.
R. Rasooly et al. / Open Journal of Immunology 1 (2011) 8-14
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CD4+ T-cells become activated when they are presented
with SAg by MHC class II molecules that are expressed
on their surface. To test this hypothesis we labeled naïve
mouse splenocyte cells with anti CD4 fluorescein la-
beled (APC) antibody, anti MHC class II fluorescein
labeled (FITC), anti CD3 labeled (PE) and anti
labeled (pacific blue). These cells were analyzed by flow
cytometer FACS Calibur. Representative data from three
independent experiments show 22% of splenocytes are
CD3 and CD4 positive (Figure 3(a)). From this popula-
tion 3.1% are positive for CD3 and MHC class II, (Fig-
ure 3(b)). 4.2% are positive for CD4 and MHC class II
(Figure 3(c)). And 2.6% are positive for αβ TCR cells
and MHC class II (Figure 3(d)). Cell sorting increased
the concentration of this fluorescin labeled T cell sub-
type (Figure 3(e)-(h)). We also used confocal fluores-
cent microscopy (Figure 3(i)) and demonstrated that
these highly purified CD4+ T cells are double labeled
with anti-CD4 antibody (labeled with APC (red) and
anti-MHC class II is labeled with FITC (green), sug-
gesting these murine CD4+ T cells express MHC class II.
3.4. Expansion of CD4+ T Cells Expressing
MHC Class II
We performed an ex vivo assay that studied long term
expansion of this cell and demonstrated that isolated
CD4+ T cells expressing MHC class II can proliferate
without using autologous APCs, and can be expanded
with immunomagnetic beads conjugated with costimu-
latory signals anti-CD28 mAb and T cell activation anti-
CD3 mAb. Without this antibody the cells did not pro-
liferate. Our result also shows that the exponential pro-
liferation of this CD4 + T cell was maintained only for 13
days with an expansion rate of 40-fold (Figure 4(a)).
Flow cytometry indicated that during this expansion time
CD4+ T cells expressed high levels of MHC class II
molecule on their surface (Fi gure 4(b)).
Our studies demonstrate for the first time a subtype of
mouse naïve CD4+ T cells express MHC class II mole-
cules on the cell surface. We showed that SEA was able
to induce high T cell proliferation in dose dependent
manner on both negatively and positively selected mouse
naïve CD4+ T cells. The proliferative response of these
selected CD4+ T cell was similar to the response from
splenocytes. SEA was able to induce CD4+ T cell pro-
liferation even in the absence of APCs. This may suggest
that the safety mechanism requiring cellular interaction
between two different types of cells, accessory cell and T
cell does not occur in the response to SAg, consequently
inducing T cell over-activation with massive cytokine
Treatment with neutralizing anti MHC class II anti-
body totally inhibits the proliferation of these CD4+ T
cells in the presence of SEA. These data suggest our
CD4+ T cells were able to present SEA via MHC class II
and provide sufficient accessory signals to themselves or
neighboring CD4+ T cells, triggering proliferation. Con-
sequently, they performed the roles of both professional
APCs and T cells. This may suggest that this T cell may
(a) (b)
Figure 4. Expansion of CD4+ T cell expressing MHC class II. Naïve CD4+ T cells expressing MHC class II molecule were iso-
lated from C57BL/6 mouse splenocytes by FACS Calibur. The purified Naïve CD4+ T cells were cultured in 96 well microplates.
At day 0, 7, 10, 13 and 17, cells were stimulated with anti-CD3/anti-CD28 mAb-coated beads and counted using the trypan blue
dye exclusion test to evaluate the fold increase in their numbers. Error bars represent standard errors and n = 3.
R. Rasooly et al. / Open Journal of Immunology 1 (2011) 8-14
Copyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/OJI/
(a) (b)
Figure 5. The current model (a) and the proposed model (b in addition to a) explain how SEA induces T cell proliferation. The
current model suggests that SAg binds to two molecules on two separate cells; the V-
portion of the TCR and the MHC class
II on APC forms a bridge between the T cell and APC induces proliferation to large number of T cells. The proposed mecha-
nism suggests that T cells express both molecules; MHC class II and TCR. Therefore, activation by SAg may require only one
type of cell performing the role of both APC and T cell. SAg binds to both molecules in neighboring T cells or to both the
TCR and MHC class II on the same cell causing massive T cell proliferation.S
play a role as a sensor cell and first line of host defense
against S. aureus infection.
Our findings demonstrate that subtype of CD4+ T cells
express MHC class II and may act as professional APC,
process SAg and pr esen t th em to n e ighbo ring T cells and
induce CD4+ T cell proliferation even in the absence of
macrophages, dendritic cells or B lymphocytes. This ob-
servation may change the interpretation of earlier ex-
periments that used fixed APCs that are metabolically
incapable to uptake and process the superantigens, but
were able to present SEs and activate T cells. Therefore,
the question as to whether processing of SEs is not re-
quired was not addresse d by t he pre vi ous st u di es.
White et al. [15] and Fleischer et al. [16] demon-
strated that T cell response to SEA are not MHC class II
restricted and that mouse TCR can recognize non host
APC expressing MHC class II alleles from different spe-
cies. However, these authors did not tak e into considera-
tion that CD4+ T cells that express MHC class II mole-
cules on their cell surface can act as APCs. Therefore,
their experimental data cannot evaluate whether MHC
restriction is violated in response to SEs.
In conclusion the paradigm (Figure 5(a)) that sug-
gests the only possible mechanism that SAg induces T
cell proliferation is by binding to two separate cells,
APC and T-cell, may be need to be revised. Our revised
model (Figure 5(b)) suggests that alongside the above
mechanism SAg may be able to induce T cell prolifera-
tion by binding to only one type of CD4+ T-cell express-
ing MHC class II. Performing the role of both accessory
cell and T cell, these cells present SAg via MHC class II
to themselves or neighboring CD4+ T-cells, triggering
nonspecific massive T-cell proliferation. The revised
model offers further insight into the in vivo mechanism
of SAg activity.
We thank Anne Bates for her help with confocal microscopy and
Daphne Tamar and Sharon Abigail for helpful discussions.
[1] Dinges, M.M., Orwin, P.M. and Schlievert, P.M. (2000)
Exotoxins of Staphylococcus aureus. Clinical Microbio-
R. Rasooly et al. / Open Journal of Immunology 1 (2011) 8-14
Copyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/OJI/
logy Reviews, 13, 16-34.
[2] Hu, D.L., Omoe, K., Sashinami, H., Shinagawa, K. and
Nakane, A. (2009) Immunization with a nontoxic mutant
of staphylococcal enterotoxin A, SEAD227A, protects
against enterotoxin-induced emesis in house musk
shrews. Journal of Infectious Diseases, 199, 302-310.
[3] Hui, J., Cao, Y., Xiao, F., Zhang, J., Li, H. and Hu, F.
(2008) Staphylococcus aureus enterotoxin C2 mutants:
biological activity assay in vitro. Journal of Industrial
Microbiology and Biotechnology, 35, 975-980.
[4] Jappe, U. (2000) Superantigens and their association with
dermatological inflammatory diseases: Facts and hy-
potheses. Acta Dermato-Venereologica, 80, 321-328.
[5] Kasper, K.J., Xi, W., Nur-Ur Rahman, A.K., Nooh, M.M.,
Kotb, M., Sundberg, E.J., Madrenas, J. and McCormick
J.K. (2008) Molecular requirements for MHC class II
alpha-chain engagement and allelic discrimination by the
bacterial superantigen streptococcal pyrogenic exotoxin
C. The Journal of Immunology, 181, 3384-3392.
[6] Rasooly, R. and Do. P.M. (2009) In vitro cell-based assay
for activity analysis of staphylococcal enterotoxin A in
food. FEMS Immunology and Medical Microbiology, 56,
172-178. doi: 10.1111/j.1574-695X.2009.00561.x
[7] Marrack, P. and Kappler, J. (1990) The staphylococcal
enterotoxins and their relatives. Science, 248, 705-711.
[8] Woodland, D. L. and Blackman, M.A. (1993) How do
T-cell receptors, MHC molecules and superantigens get
together? Immunol Today, 14, 208-212.
[9] Tsang, J.Y., Chai, J.G. and Lechler, R. (2003) Antigen
presentation by mouse CD4+ T cells involving acquired
MHC class II:peptide complexes: another mechanism to
limit clonal expansion? Blood, 101, 2704-2710.
[10] Schooten, E., Klous, P., van den Elsen, P.J. and Holling,
T.M. 2005. Lack of MHC-II expression in activated
mouse T cells correlates with DNA methylation at the
CIITA-PIII region. Immunogenetics, 57, 795-799.
[11] Li, W., Kim, M.G., Gourley, T.S., McCarthy, B.P.,
Sant’Angelo, D.B. and Chang C.H. (2005) An alternate
pathway for CD4 T cell development: thymocyte-ex-
pressed MHC class II selects a distinct T cell population.
Immunity, 23, 375-386.
[12] Chang, C.H., Hong, S.C., Hughes, C.C., Janeway Jr., C.A.
and Flavell, R.A. (1995) CIITA activates the expression
of MHC class II genes in mouse T cells. International
Immunology, 7, 1515-1518. doi:10.1093/intimm/7.9.1515
[13] Li, W., Sofi, M.H., Yeh, N., Sehra, S., McCarthy, B.P.,
Patel, D.R., Brutkiewicz, R.R., Kaplan, M.H. and Chang.
C.H. (2007) Thymic selection pathway regulates the ef-
fector function of CD4 T cells. The Journal of Experi-
mental Medicine, 204, 2145-2157.
[14] Stephensen, C.B., Rasooly, R., Jiang, X., Ceddia, M.A.,
Weaver, C.T., Chandraratna, R.A., Bucy, R.P. (2002) Vi-
tamin a enhances in vitro Th2 development via retinoid
X receptor pathway. The Journal of Immunology, 168,
[15] White, J., Herman, A., Pullen, A.M., Kubo, R., Kappler,
J.W. and Marrack, P. (1989) The V beta-specific superan-
tigen staphylococcal enterotoxin B: Stimulation of ma-
ture T cells and clonal deletion in neonatal mice. Cell 56,
27-35. doi:10.1016/0092-8674(89)90980-X
[16] Fleischer, B., Schrezenmeier, H. and Conradt, P. (1989) T
lymphocyte activation by staphylococcal enterotoxins:
role of class II molecules and T cell surface structures.
Cellular Immunology, 120, 92-101.