Major histocompatibility complex/ Immunology

1. MADURAI KAMRAJ UNIVERSITY
SCHOOL OF BIOTECHNOLOGY

6.  Group of complex genes
 Situated on the short arm of chromosome 6
in humans.
 These molecules are glycoproteins.
 Play an important role in the regulation of
the adaptive immune response.
 Autoimmune blistering disease provides an
ideal model for studying the role of MHC in
autoimmunity.

7.  In humans, it contains more than 200 genes
 The system is called H2 in mice ,( first
recognized in 1937 as a barrier to
transplantation in mice).
 Called HLA (human lymphocyte antigen) in
humans,( first discovered through antigenic
differences between white blood cells from
different individuals).

8.  Class I MHC contains three genes called HLA-
A, B, and C; proteins from these genes are
expressed on almost all cells.
 Class II MHC genes are called HLA-DR, DQ,
and DP; their proteins are expressed on
antigen-presenting macrophages, dendritic
cells and B cells.

10. similarity in structure between the two classes

13.  T cells recognize foreign antigens in the form
of short peptides that have been processed
and displayed on the cell surface bound to
MHC-I or MHC-II molecules.
 Antigens are often categorized according to
whether they are derived from
 (1) viruses, intracellular bacteria, or protozoan
parasites (endogenous pathogens); or
 (2) exogenous pathogens that replicate outside of
the cell.

15.  Intracellular antigens are presented to T cells by any
nucleated cell because MHC-I expression is ubiquitous.
 In contrast, exogenous antigens are taken up by
professional APCs, which process the antigens and present
them in the context of MHC-II.

16.  Endogenous antigens, including misfolded
proteins and pathogen-derived peptides, are
processed by the proteasome.
 This complex of proteases typically generates
peptides of four to twenty amino acids with
a hydrophobic carboxy terminus.
 After trimming of the peptide by cytosolic
proteases, the antigenic peptides are translocated
to the endoplasmic reticulum by the transporters
associated with antigen processing (TAP1 and
TAP2 molecule).
 Meanwhile, a new MHC-I molecule is being
synthesized in the endoplasmic reticulum.

18.  As it folds, it is bound by calnexin, which is
then replaced by calreticulin and b2
 The new MHC-I molecule associates with the
MHC-I peptide loading complex.

19.  Tapasin physically links the MHC-I molecules
and the TAP transporters. As the peptide
enters from the cytosol, the cleft of the class I
molecule receives it and the peptide-bound
MHC-I molecule dissociates from the peptide-
loading complex and is recruited to the cell
surface.
 This complex machinery has several quality-
control steps, such that MHC-I molecules that
fail to assemble properly are degraded.
 Ultimately, the peptide presented on MHC-I
molecule will stimulate a CD8 T cell response

22. Exogenous antigens
 Exogenous antigens are processed quite differently.
 Bacterial proteins are cleaved by proteases, cathepsins, and metalloproteases
in the acid environment of the endocytic pathway.
 Meanwhile, MHC-II molecules assemble in the endoplasmic reticulum with
another molecule called the invariant chain (li). The newly synthesized
molecules transit the endoplasmic reticulum and the Golgi apparatus.
 After passage of the li-loaded MHC-II-DM complex through the Golgi into the
late endosomes, the invariant chain is cleaved by acid proteases, leaving a
residual peptide referred to as the CLass II-associated Invariant chain Peptide
(CLIP) in the MHC-II cleft.
 CLIP occludes the MHC-II cleft and prevents peptides from loading until the
molecule is in the lysosomal or late endosomal compartment containing the
peptides.
 At that point, HLA-DM molecules remove CLIP from the cleft and stabilize the
molecule while the peptide is loaded into the cleft.
 HLA-DO molecules can also facilitate this process in some settings.
 The fully assembled and loaded MHC-II molecule is recruited to the surface and
serves to stimulate predominantly CD4 positive T cells (Figure 6B and Figure 7).

23. DIAGRAMATIC PRESENTATION OF EXTRACELLULAR OR EXOGENOUS
ANTIGENS

24. Endogenous antigens are generally presented to CD8þ T cells (left
panel), and exogenous antigens are generally presented to CD4þ T
cells

25. SUBMITTED BY:
AMREEN KHAN
MSc SEM I