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MHC Molecule

The document provides information about the major histocompatibility complex (MHC). It discusses that MHC molecules are found on nucleated cells and play a key role in immunity by presenting antigens to T cells. It describes the structure and functions of class I and class II MHC molecules, including their roles in antigen presentation to CD8+ and CD4+ T cells, respectively. The document also notes that MHC genes are highly polymorphic and located on chromosome 6, and their products allow for recognition of foreign tissue during transplantation.

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Shah NAWAZ
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0% found this document useful (0 votes)
43 views45 pages

MHC Molecule

The document provides information about the major histocompatibility complex (MHC). It discusses that MHC molecules are found on nucleated cells and play a key role in immunity by presenting antigens to T cells. It describes the structure and functions of class I and class II MHC molecules, including their roles in antigen presentation to CD8+ and CD4+ T cells, respectively. The document also notes that MHC genes are highly polymorphic and located on chromosome 6, and their products allow for recognition of foreign tissue during transplantation.

Uploaded by

Shah NAWAZ
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as PPTX, PDF, TXT or read online on Scribd
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Advances in Immunology

MLTAI-1201
Course Incharge: AdeelShahid

Lecturer

UIMLT, FAHS
Major Histocompatibility
Complex
Objectives

Introduction of MHC
Structure of MHC
Functions of MHC
Major Histocompatibility Complex

 The genetic capability to mount an immune


response is linked to a group of molecules
originally referred to as human leukocyte
antigens (HLA).
Major Histocompatibility Complex

 These antigens are also known as MHC


molecules, because they determine whether
transplanted tissue is histocompatible and thus
accepted or recognized as foreign and rejected.
Function of MHC

 MHC molecules are actually found on all


nucleated cells in the body, and they play a
pivotal role in the development of both humoral
and cellular immunity.
Function of MHC

 Their main function is to bring antigen to the cell


surface for recognition by T cells, because T-cell
activation will occur only when antigen is
combined with MHC molecules.
Function of MHC

 Clinically, they are relevant, because they may


be involved in transfusion reactions, graft
rejection, and autoimmune diseases.
Genes Coding for MHC Molecules

 The MHC system is the most polymorphic


system found in humans
 Genes coding for the MHC molecules in humans
are found on the short arm of chromosome 6 and
are divided into three categories or classes.
Genes Coding for MHC Molecules

 Class I molecules are coded for at three different


locations or loci, termed A, B, and C.
 Class II genes are situated in the D region, and
there are several different loci, known as DR,
DQ, and DP.
Genes Coding for MHC Molecules

 Between the class I and class II regions on


chromosome 6 is the area of class III genes,
which code for complement proteins and
cytokines such as tumor necrosis factor
The major histocompatibility complex
Genes Coding for MHC Molecules

 The MHC system is polymorphic, because there


are so many possible alleles at each location.

For example, at least 580 different alleles of HLA-


A, 921 alleles of HLA-B, and 312 alleles of HLA-
C have been identified.
Genes Coding for MHC Molecules

 The probability that any two individuals


will express the same MHC molecules is
very low.
Genes Coding for MHC Molecules

 An individual inherits two copies of


chromosome 6, and thus there is a possibility of
two different alleles for each gene on the
chromosome, unless that person is homozygous
(has the same alleles) at a given location.
Structure of Class I Molecules
 Each of the MHC genes codes for a protein
product that appears on cell surfaces.
 All the proteins of a particular class share
structural similarities and are found on the same
types of cells.
Class I MHC Molecule

 Class I MHC molecules are expressed on all


nucleated cells, although they differ in the level
of expression.
 They are highest on lymphocytes and low or
undetected on liver hepatocytes, neural cells,
muscle cells, and sperm.
Class I MHC Molecule

 Additionally, HLA-C antigens are expressed at a


lower level than HLA-A and HLA-B antigens.
 Each class I antigen is a glycoprotein dimer,
made up of two noncovalently linked
polypeptide chains.
Class I MHC Molecule

The α chain has a molecular weight of 45,000. A


lighter chain associated with it, called a β2–
microglobulin, has a molecular weight of 12,000
and is encoded by a single gene on chromosome 15
that is not polymorphic.
Class I MHC Molecule

 The α chain is folded into three domains, α1, α2,


and α3, and it is inserted into the cell membrane
via a transmembrane segment that is
hydrophobic.
Class I MHC Molecule

 The three external domains consist of about 90


amino acids each, the transmembrane domain
has about 25 hydrophobic amino acids along
with a short stretch of about 5 hydrophilic amino
acids.
Class I MHC molecule
Class I MHC Molecule

 β2–microglobulin does not penetrate the cell


membrane, but it is essential for proper folding of the
α chain.
Class I MHC Molecule

 α1 and α2 domains each form an alpha helix and


that these serve as the walls of a deep groove at
the top of the molecule that functions as the
peptide-binding site in antigen recognition.
Class I MHC Molecule

 This binding site is able to hold peptides that are


between 8 and 10 amino acids long.
 The α3 region reacts with CD8 on cytotoxic T
cells.
Class I MHC Molecule

 Another group of molecules called the non


classical class I antigens are designated E, F, and
G.
Class I MHC Molecule

 This group of molecules, except for G, are not


expressed on cell surfaces and do not function in
antigen recognition but may play other roles in
the immune response.
Class I MHC Molecule

G antigens are expressed on trophoblast cells during


the first trimester of pregnancy and are thought to
help ensure tolerance for the fetus by protecting
placental tissue from the action of NK cells.
Class I MHC Molecule
Class II MHC molecule

 The occurrence of class II MHC molecules is much


more restricted than that of class I, because they are
found primarily on antigen-presenting cells, which
include B lymphocytes, monocytes, macrophages,
and dendritic cells.
Class II MHC Molecule

 The major class II molecules—DP, DQ, and DR


—consist of two non covalently bound
polypeptide chains that are both encoded by
genes in the MHC complex.
Class II MHC Molecule

 DR is expressed at the highest level


 The DR β gene is the most highly polymorphic,
as 18 different alleles are known.
Class II MHC Molecule

 Both the α chain, with a molecular weight of 33,000,


and the β chain, with a molecular weight of 27,000, are
anchored to the cell membrane.
 Each has two domains, and it is the α1 and the β1
domains that come together to form the peptide-
binding site.
Class II MHC molecules

 However, both ends of the peptide-binding cleft


are open, and this allows for capture of longer
peptides than is the case for class I molecules.
Class II MHC molecules

 Three other class II genes have been described—


DM, DN, and DO, called non classical class II
genes.
 Products of these genes play a regulatory role in
antigen processing.
Class II MHC structure
Antigen presentation

 The main role of the class I and class II MHC


molecules is to bind peptides within cells and
transport them to the plasma membrane, where T cells
can recognize them in the phenomemon known as
antigen presentation.
Antigen presentation

 The two main classes of these molecules have


evolved to deal with two types of infectious agents:
those that attack cells from the outside (such as
bacteria) and those that attack from the inside (viruses
and other intracellular pathogens).
Antigen presentation

 Class I molecules are thus the watchdogs of viral,


tumor, and certain parasitic antigens that are
synthesized within the cell, while class II
molecules stimulate CD4 T cells in the case of
bacterial infections or the presence of other
material that is endocytosed by the cell.
Antigen presentation

 The chemistry of the MHC antigens controls


what sorts of peptides fit in the binding pockets.
Learning Outcomes

At the end of the lecture, students have learnt about


 Major histocompatibility complex
 Classification and structure of MHC
 Role of MHC in antigen presentation
Reference books

1. Abbas, A.K., Lichtman, A.H.H., and Pillai, S.


Cellular and Molecular Immunology, 8th
Edition.

2. Jawetz, Melnick, & Adelberg’s Medical


Microbiology, Twenty-Sixth Edition
Thank You

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