1. MAJOR
HISTOCOMPATIBILITY
COMPLEX (MHC)
BY
TRUPTIMAYEE MOHANTY

2. OBJECTIVES
To discuss briefly about what is MHC
molecule.
How it contribute to our immune system
Types of MHC molecules
Its significance in our immune system

3. CONTENTS
1. INTRODUCTION
2. HISTORY
3. CLASS OF MHC MOLECULES
4. STRUCTURE OF MHC
5. CELLULAR DISTRIBUTION OF MHC
MOLECULES
6. CONTRIBUTIONS TO THE IMMUNE
SYSTEM
7. CONCLUSION
8. REFERENCE

4. INTRODUCTION
 Major Histocompatibility Complex
(MHC) is a tightly linked cluster of
genes present in every vertebrate
species.
 Plays important roles in intracellular
recognition and in discrimination
between self and non-self.
 Participates in development of both
humoral and cell mediated immune
response.

5.  MHC is located in short arm of
chromosome no. 6 in humans and on
chromosome no. 17 in mice.
 It is referred to as the HLA (Human
Leucocyte Antigen) complex in humans and
H-2 (histocomatibility-2) in mice.
 MHC is highly polymorphic and shows
genetic polymorphism.
 MHC genes are co-dominantly expressed.
 Every individual has an almost unique array
of inherited MHC genes.

6. HISTORY
 The concept that the rejection of
foreign tissue is the result of an
immune response to cell-surface
molecules, now called
histocompatibility antigens,
originated from the work of Peter
Gorer in the mid-1930s.
 Snell called the genes as
histocompatibility genes and was
awarded the Nobel prize in 1980.

7. CLASSES OF MHC MOLECULES
 There are following classes of MHC genes:
 Class 1 MHC genes
 Class 2 MHC genes
 Class 3 MHC genes
 MHC class 1 and 2 genes encode the
antigen-presenting molecules.
 MHC class 3 genes encode several
secreted proteins i.e., components of
the complement system( C2,C4) and
molecules related with inflammation or
heat shock proteins.

8. STRUCTURE OF CLASS-1 MHC MOLECULE
 Found on the surface of all nucleated cells.
 Each MHC class 1 gene codes for a transmembrane
glycoprotein (43k Da) i.e., a chain which has 3
extracellular domains a1, a2,a3
 a3 domain interacts with CD8 membrane molecule
present on Tc cells.
 Another small invariant polypeptide associated non-
covalently called – b2 microglobulin (b2m: mol. Wt.
12 k Da).
 a3 is the CD8 binding site.
 it has a peptide binding cleft between a1 & a2.

9. STRUCTURE OF CLASS 1 MHC MOLECULE

10. STRUCTURE OF CLASS 2 MHC MOLECULES
 It has 2 different polypeptide chains, an a
chain(33 kDa) and a b chain(28 kDa).
 Each chain contains 2 external domains
i.e., a1 & a2 domains in one chain and b1&
b2 in other.
 a2 & b2 domains has the antigen binding
cleft for the processed antigen.

11. STRUCTURE OF CLASS 2 MHC
MOLECULES

12. CELLULAR DISTRIBUTION OF
MHC MOLECULES
 MHC molecules are highly found in
lymphocytes that comprises 1% of the total
plasma membrane of the cell.
 They are lowest in fibroblasts, muscle cells,
liver hepatocytes and neural cells.
 They are absent in neurons and sperm
cells(at certain stage of differentiation).

13. CONTRIBUTION OF MHC TO THE IMMUNE
SYSTEM
1.Class-1 MHC-peptide interaction

14. CLASS-2 MHC-PEPTIDE
INTERACTION

15. 2. ROLE IN THYMIC SELECTION OF T-
CELLS:
T-cell development occurs from common lymphoid
progenitor cells. Initially they are called as pro T-cells
or DN Cells(CD4- ,CD8-). They convert from DN1-
DN4 and become DP(CD4+,CD8+) and then
undergoes positive ad negative selection and
interacts with self MHC molecules expressed on
epithelial cells in thymic cortex and results in
differentiation of DP cells.

17. 3. GRAFT REJECTION DURING
TRANSPLANTATION:
• Graft rejection is a phenomenon in which
transplanted tissue/cells expressing donor-derived
MHC determinants that are disparate from those
of the host are destroyed by immune-mediated
mechanisms.
• Mostly it is associated with allograft rejection as
here the grafting occurs between different species.

18. CONCLUSION
MHC is a complex, a set of genes inherited as
a unit. It codes for 3 major categories of cell
surface transmembrane molecules i.e., MHC-1
, MHC-2 and MHC-3. MHC molecules play a
crucial role in the response of T-cells to
antigens that are taken into or live inside cells
of the body.

19. REFERENCE
1. https://www.sciencedirect.com
2. Pranav Kumar and Usha Mina, Life Science:
Fundamentals and practice, 6th edition
(2017), Pathfinder Publication , page no 477-
480
3. Kuby Janis, Immunology (2003), 5th edition,
W.H. Freeman and company, New York,
page 160-182
4. Dulsy Fatima and N. Arumngam (2013), 4th
edition, Saras Publication, Camp wad
perivilaki, Kanyakumari, page 481-502
5. www.wikipedia.in
6. www.ncbi.nlm.gov.in

20. THANK YOU !!!