The presentation is on two main topics of immunology 1. Major Histocompatibility Complex (MHC) 2. Superantigens

1. SUBMITTED BY:
Jasleen Rajpal
Deeksha Singh
Ria Sara Thomas
Priyanka Mathur
Parul Yadav
{btech biotech
6th semester}
Topics:
1. Major histocompatibility complex
2. superantigens
SUBMITTED TO:
Ms. Ravneet Chug
Faculty immunology

2. INTRODUCTION
MAJOR
HISTOCOMPATIBLITY
COMPLEX

3. 1.MHC
{Major Histocompatility Complex}
Every mammalian species studied till date
possesses a tightly linked cluster of genes, the
major histocompatibility complex, whose products
play roles in intercellular recognition and in
discrimination between self and non self.
 The MHC participates in the development of
both humoral and cell mediated immune
responses.
most T cells recognize antigen only when it is
combined with an MHC molecule.

4. For this reason, the MHC partly determines the
response of an individual to antigens of infectious
organisms, and it has therefore been implicated
in the susceptibility to disease and in the
development of autoimmunity.
The recent understanding that natural killer cells
express receptors for MHC class I antigens and
the fact that the receptor–MHC interaction may
lead to inhibition or activation expands the known
role of this gene family .

5. The major histocompatibility complex is a
collection of genes arrayed within a long
continuous stretch of DNA on chromosome 6 in
humans and on chromosome 17 in mice. The
MHC genes are organized into regions encoding
three classes of molecules :
Class I MHC genes encode glycoproteins
expressed on the surface of nearly all nucleated
cells; the major function of the class I gene
products is presentation of peptide antigens to TC
cells.
Class II MHC genes encode glycoproteins
expressed primarily on antigen-presenting cells
(macrophages, dendritic cells,and B cells),where

6. The class I and class II MHC molecules have
common structural features and both have roles
in antigen processing.
By contrast, the class III MHC region, which is
flanked by the class I and II regions, encodes
molecules that are critical to immune function but
have little in common with class I or II molecules.
 Class III products include the complement
components C4, C2, BF, and inflammatory
cytokines, including tumor necrosis factor (TNF)
and heat-shock proteins.
MHC are highly polymorphic; that is, many
alternative forms of the gene, or alleles, exist at
each locus among the population

7. POINTS TO PONDER
Human MHC class I and II are also
called human leukocyte antigen (HLA).
 To clarify the usage, some of the biomedical
literature uses HLA to refer specifically to the
HLA protein molecules and reserves MHC for
the region of the genome that encodes for this
molecule, but this is not a consistent
convention.
The most studied HLA genes are the nine
classical MHC genes: hla-a, hla-b, hla-c, hla-
dpa1, hla-dpb1, hla-dqa1, hla-dqb1, hla-dra,
and hla-drb1. In humans, the MHC gene

8. The class I and class II gene products shown in
this figure are considered to be the classical MHC
molecules. The class III gene products include
complement (C) proteins and the tumor necrosis

9. NATURE OF MHC
1. Polygenic – 9 main gene
2. Polymorphic- multiple alleles for each
genes
3. Co dominant – both maternal and paternal
alleles are expressed equally

11. Class I MHC molecules
STRUCTURE
 Contain a 45-kilodalton (kDa) alpha chain
associated non covalently with a 12-kDa beta
2-microglobulin molecule.
 The alpha chain is a transmembrane
glycoprotein encoded by polymorphic genes
within the A, B, and C regions of the human
HLA complex and within the K and D/L regions
of the mouse H-2 complex .
 Beta 2-Microglobulin is a protein encoded by a
highly conserved gene located on a different
chromosome.

13.  The alpha chain is anchored in the plasma
membrane by its hydrophobic
transmembrane segment and hydrophilic
cytoplasmic tail.
 Structural analyses have revealed that the α
chain of class I MHC molecules is organized
into three external domains (α1, α2, and α3),

14. Each containing approximately 90 amino acids;
a transmembrane domain of about 25
hydrophobic amino acids followed by a short
stretch of charged (hydrophilic) amino acids; and
a cytoplasmic anchor segment of 30 amino acids.
The β2-microglobulin is similar in size and
organization to the α3 domain; it does not contain
a transmembrane region and is noncovalently
bound to the class I glycoprotein.
The α3 domain and β2-microglobulin are
organized into two β pleated sheets each formed
by antiparallel β strands of amino acids

15. FUNCTION
Class I MHC molecules bind peptides and
present them to CD8+ T cells.
These peptides are derived from
endogenous intracellular proteins that are
digested in the cytosol and then transported to
cisternae of the ER, where they interact with
class I MHC molecules.
This process, known as the cytosolic or
endogenous processing pathway

16. Class II MHC molecules
STRUCTURE
 Contain two different polypeptide chains, a 33-kDa
α chain and a 28-kDa β chain, which associate by
non covalent interactions.
 Like class I α chains, class II MHC molecules are
membrane-bound glycoproteins that contain
external domains, a transmembrane segment, and
a cytoplasmic anchor segment.
 Each chain in a class II molecule contains two
external domains: α1 and α2 domains in one chain
and β1 and β2 domains in the other.
 The membrane-proximal α2 and β2 domains, like
the membrane-proximal α3/β2-microglobulin
domains of class I MHC molecules, bear sequence

18.  The membrane-distal portion of a class II molecule
is composed of the α1 and β1 domains and forms
the antigen binding cleft for processed antigen.
 The class II molecule lacks the conserved residues
that bind to the terminal residues of short peptides
and forms instead an open pocket.

19. REACTION TO BACTERIA
Because class II MHC is loaded with
extracellular proteins, it is mainly concerned
with presentation of extracellular pathogens
(eg, bacteria that might be infecting a wound).
Class II molecules interact mainly with
immune cells, like the T helper cell (TCD4+) .
Which then help to trigger an appropriate
immune response which may include
localized inflammation and swelling due to
recruitment of phagocytes or may lead to a full-
force antibody immune response due to
activation of B cells.
Besides antigen presentation, growing

21. SUPER ANTIGEN
Superantigens are class of antigen that causes non-
specific activation of T-cells which further causes
polyclonal activation of T-cell and cytokine release.
Superantigens are produced by some pathogenic
viruses and bacteria as a defense mechanism against
immune system. Compared to normal antigen induced
T-cell response where 0.0001-0.001% of the body’s
cell are activated these superantigens are capable of
activating up to 25% of body’s T-cell
Large number of activated T-cell produce a massive
immune response which is not specific to any
particular epitope on the S.Ag thus it undermines one
of the fundamental strength of the adaptive immune
system that is its ability to target antigen with high

22. Large number of activated T-cell release large
amount of cytokines, most important of which is IFN
gamma. The excess amount of interferon gamma in
turn activate macrophages.
The activated macrophages in turn overproduce
proinflammatory cytokines such as IL-1,IL-6 and TNF
–alpha.
TNF-alpha is particularly important as body’s
inflammatory response. In normal circumstances it is
released in low level and help the immune system to
defeat the pathogen but when it is released in high
level (due to mass T-cell activation from Sag) can
cause severe and life threatening symptoms such as
Shock and Multiple organ faliure.

23. Structure
Superantigens are produced by the bacteria
intracellularly and are release upon infection as
mature extracellular toxin,
The sequence of these toxins are similar among
different subgroup .
The 3D structure is also similar among different SAg
which result in similar functional effect among different
group.
The structure of Sags is compact and ellipsoidal and
comprise 2 domain folding pattern.
One domain has binding region for MHC-II and 2nd
domain has binding region for Tcell.
Binding
The Superantigen first bound to MHC-II and then are

24. BINDING WITH MHC-II
SAg show preference for HLADQ form of cell surface
receptor found on APC. It is alpha-beta hetrodimer of
class II MHC. Several staphylococcus SAg are capable
of crosslinking by binding with both alpha and beta
chain.
This mechanism stimulate cytokine expression and
release in APC as well as inducing the production of co-
stimulatory molecule that allow the cell to bind and
activate the T-cells.
BINDING WITH T-CELL
T-cell binding region of Superantigen bind with the
variable region on beta chain of T-cell receptor.
A particular SAg can activate large proportion of T-cell
population because humans contain only 50types of
variable region on beta chain and some superantigens

27. Treatment
Primary goal of treatment is to remove the microbe
that is producing the antigen. This is done by the
vasopressors, fluid resuscitation and antibiotics.
Our body naturally produces antibodies against some
SAg, this effect is augmented by stimulating B cell
production of these antibodies.
Synthetic antibodies and peptides are produced that
mimic the SAg binding region on MHC II, this blocks
the interaction of Sag with MHCII and prevent T cell
activation.