This PPT discusses about superantigens and their role in diseases. PPT prepared by Snehashish. M.Sc. Zoology. Please accredit the author if in use. Snehashish M.Sc. Zoology Banaras Hindu University Linked in- www.linkedin.com/in/snehashish-4257691a4

1. Superantigens
The Good, Bad & Ugly
Presented by:
Snehashish

2. Superantigen
Introduction,
Structure,
comparision with
antigens
01
Contents
Biological
Activity
Mechanism of
action, T cell
stimulation,
Effects of SAg
stimulation
02
Application
Use of SAg, in the
medical and
weaponry context
04
Diseases
Diseases caused
by SAg, Diagnosis
and Treatment
03

3. 01
Why, What, How, When Where?
Superantigens

4. In nature there has been an arms race between the
Hosts and Parasites. The host tries all it can to
escape the parasite and a parasite tries its best to
infect a host. In this toxic relationship of theirs, they
each evolve certain mechanisms to defeat each
other.
In order to avoid infection, hosts have developed
immune systems which pose a challenge to the
parasites, however certain parasites have
developed superantigens in order to evade the
hosts immune system.
Introduction
Image Credit: 1. dreamstime.com
2. istockphoto.com

5. What are Superantigens?
1. Kappler and Marrack in the year 1990 analyzed and named
a staphylococcal protein as superantigen.
2. Superantigens are of various types and originate from
microbial sources like bacteria, viruses and Mycoplasma.
3. SAg can be secreted exotoxins or membrane bound
endotoxins
4. Primarily the major purpose of superantigen is to misguide
the host’s immune system so the parasite could flourish
Image credit: Palmer, 1991

6. Structure of SAg
1. SAg are medium sized globular proteins ranging from 22
to 29kDa.
2. The N-terminal is characterized by presence of an α helix
and hydrophobic residues.
3. The C terminal has 4 Stranded β sheets which are
capped by a central α helix.
4. The 4 Stranded β sheets on the C-terminal contribute to
the super-antigenicity of the molecule.
5. The hydrophobic residues decide the lethality of the SAg

7. Super?
SUPER
MAN SUPERMAN

8. Antigens Vs Superantigens
• Antigens are processed by Antigen
presenting cells post introduction
• Antigen recognition and T cell activation Is
MHC-II restricted
• Small proportion of T cells become
activated (<0.001%) and highly regulated
response
• Superantigen are not required to
go through antigen processing
• MHC-II positive cells are required
for SAg-induced T cell activation,
but it is not MHC-II restrictive
• Massive T cell activation (20 to 30%)
and associated with serious
consequences

9. 02
Biological
Activity

11. Classically antigens are processed by Antigen
presenting cells and a small epitope is generated which
acts as a bridging molecule between the HLA complex
of APC and Tcell, the antigen binds with both vα and vβ
subunits. This interaction activates a highly regulated
signaling cascade which leads to activation of a small
number of T cells, which are specific to that antigen
presented.
However superantigen interaction with the TCR leads to
an entirely different fate. SAg have specific affinity
towards the vβ domain of the TCR which leads to
triggering of multiple signaling cascades simultaneously
resulting in activation of a very large number of T cells.
The immune response elicited is non-specific and
unregulated.
Image source:
https://www.sciencedirect.com/topics/pharmacology-toxicology-
and-pharmaceutical-science/superantigen
Mechanism of Action

12. Tcell Stimulation by
Superantigens
• In the case of superantigens, the molecule forms a strong association with the vβ subunit of TCR and
α subunit of MHC class II.
• However the SAg binds to the outside of antigen binding cleft, as a results other Tcells with the same
vβ subunit also get activated and lead to polyclonal activation of Tcells.
• As a result the cascade can activate a massive number of Tcells, almost 20 to 30% of clones get
activated. - Polyclonal Activation
• Activation of large numbers of Tcells leads to over production of cytokines which can lead to
systemic toxicity and immune suppression
• Scientists speculate that the overproduction of cytokines may prove useful to parasites as it thwarts
the antigen specific cascades of adaptive immune mechanisms.

13. Increased
Prothrombic and
Proinflammatory
activity
IL-6,
GMCSF
and E
selectin
Larger no. Of T cells
produce IL-1 AND
TNF-α leads to injury
of endothelial tissue
of blood vessels
Expression of TNF α
In response to
elevated endotoxin
activity results in
endothelial cell
death and vascular
insult
B cell stimulation leads
to formation of immune
complexes
SAg Elevated cytokines along
with bacterial toxins reduce
the threshold for shock
Stimulation

14. 03
Lets get to the Bad Part
Diseases

15. FOOD POISONING
Staphylococcus aureus has been known to be the major culprit in
food poisoning. The enterotoxins A,B,C,D,E and H are known to
cause food poisoning. The disease is characterized by emesis with
or without diarrhea along with fever. This is caused due to
infection of preformed superantigens from contaminated water
or food. The ingested superantigens trigger an inflammatory
response in the gut mucosa leading to neutrophil infiltration.
Unknown cytokines, produced by neutrophils, cause systemic
discomfort like fever and repeated vomiting.
Image Credit: https://www.cdc.gov/foodsafety/symptoms.html

16. Bacteria like Streptococcus pyogens and
Staphylococcus aureus release exotoxins which are
known to have superantigenic properties. Toxic
Shock Syndrome refers to an acute fatal illness
characterized by very high fever, erythematous
rash, hypotension and involvement of three or
more organ systems.
In the worst case scenario a patient might suffer
from either acute renal or liver failure or
pulmonary edema caused due to rupture in
vascular tissues but all in all the result in such
cases is death.
Toxic Shock Syndrome
Image Credit: https://images.app.goo.gl/rceDrBfi4nXBX4nSA

17. Kawasaki
syndrome
Kawasaki syndrome is one of the leading causes of
heart disease in infants and children below the age
of 5. This disease is caused after the introduction of
Streptococcal or Staphylococcal toxins in babies.
The T cell stimulation caused by the SAg leads to
release of cytokines like IL-1, IL-6, IL-10, GM-CSF and
E-SELECTIN eliciting exaggerated prothrombic and
inflammatory responses which results in
endothelial activation. The activated endothelial
cells lead to vascular insult. Multiple vasculitis cause
severe heart problems. Image credit: https://www.ckn.org.au/content/dynamed-plus-
%E2%80%93-featured-topic-kawasaki-disease

18. Diagnosis and
Treatment
• A small fraction of Superantigen or enterotoxin can be obtained from cultures of
the bacteria isolated from the patient
• The isolated protein can be analyzed to determine the structure and origin
• In staphylococcal infection, antibiotic like Clindamycin can help eliminate the
bacteria.
• In severe conditions IV transfer of IgG has shown success in patients with TSS
• In the case of TSS corticosteroid therapy has shown some promising results

19. 04
Application

20. SAg as Cancer
Therapeutic Agents
Genetically engineered staphylococcal enterotoxin A (SEA) was
fused with a Fab fragment specific for tumor cells in the lung of
rabbits which activated 10% of T-cells, almost the strength of
activation of a toxic superantigen, and targeted these cells
against antigen positive tumor cells.
Fab fragment specifically bound to these tumor cells ,while SEA
bound to MHC I on the tumor cells. This stimulated the immune
response against the tumor cells and activated T cells to induce
cytotoxicity and kill the tumor cells.
SAg
• Bind with APC
• Bind with TCR
T-Cell
• Co-stimulation
• Cytokines
Tcyt
• cytotoxicity
• Killing of
tumor cells

21. Superantigen as a
global threat
In recent years the risk of bioterrorism
has increased due to emergence of
biohackers.
The possibility of the use of
Staphylococcal SAg as bioweapon has
been a concern for intelligence agencies
across the globe.
This leaves us with a question?
Image Credit: https://99percentinvisible.org/article/biohazard-symbol-designed-to-be-
memorable-but-meaningless/

22. Nature has a Pandora’s Box
of resources with equal
potential for creation and
destruction, which side are
we on?

23. Conclusion:
In nature the tug of war between hosts and parasites is a never
ending one. This battle has been fought between two competitors
with equal abilities hence a balance is maintained. When either of
the combatants tries to go few steps ahead, the relationship is
disturbed with catastrophic outcomes for both. Respecting nature is
the best way to ensure that we as a species survive longer. The more
hygienic we are and the less we exploit medicine, the less likely we
are to encounter disruptions such as these.

24. References
• Ahanotu, Ejem & Alvelo-Ceron, Damaris & Ravita, Timothy & Gaunt, Ed. (2006). Staphylococcal Enterotoxin B as a Biological
Weapon: Recognition, Management, and Surveillance of Staphylococcal Enterotoxin. Appl. Biosafety. 11. 120-126.
10.1177/153567600601100303.
• Dennis K. Flaherty (2012). urface Interactions Between T Cells and Antigen-Presenting Cells. Immunology for Pharmacy,
Mosby,Pages 45-54, ISBN 9780323069472,
• Janik, E., Ceremuga, M., Saluk-Bijak, J., & Bijak, M. (2019). Biological Toxins as the Potential Tools for Bioterrorism. International
journal of molecular sciences, 20(5), 1181. https://doi.org/10.3390/ijms20051181
• Owen, J. A., Punt, J., Stranford, S. A., Jones, P. P., & Kuby, J. (2009). Kuby immunology. New York: W.H. Freeman.pp367-368
• Drake, C.G., Kotzin, B.L. Superantigens: Biology, immunology, and potential role in disease. J Clin Immunol 12, 149–162 (1992).
https://doi.org/10.1007/BF00918083
• Proft, T., & Fraser, J. D. (2003). Bacterial superantigens. Clinical and experimental immunology, 133(3), 299–306.
https://doi.org/10.1046/j.1365-2249.2003.02203.x
• Ross, A., & Shoff, H. W. (2021). Toxic Shock Syndrome. In StatPearls. StatPearls Publishing.
• Schlievert P. M. (1993). Role of superantigens in human disease. The Journal of infectious diseases, 167(5), 997–1002.
• Vergis, N., & Gorard, D. A. (2007). Toxic shock syndrome responsive to steroids. Journal of medical case reports, 1, 5.
https://doi.org/10.1186/1752-1947-1-5
• Waterhouse, A., Bertoni, M., Bienert, S., Studer, G., Tauriello, G., Gumienny, R., Heer, F.T., de Beer, T.A.P., Rempfer, C., Bordoli,
L., Lepore, R., Schwede, T. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res. 46,
W296-W303 (2018)

25. THANK YOU

26. CREDITS: This presentation template was created by Slidesgo,
including icons by Flaticon, infographics & images by Freepik
and illustrations by Stories
Thanks!
Do you have any questions?
snehashishsparx@gmail.com