Major Histocompatibility Complex
T and B both cells use surface molecules to recognize antigen, they accomplish this in very
different ways. In contrast to antibodies or B-cell receptors, which can recognize an antigen
alone, T-cell receptors only recognize pieces of antigen that are positioned on the surface of
other cells. These antigen pieces are held within the binding groove of a cell surface protein
called the major histocompatibility complex (MHC) molecule, encoded by a cluster of
genes collectively called the MHC locus.
These fragments are generated inside the cell following antigen digestion, and the complex
of the antigenic peptide plus MHC molecule then appears on the cell surface. MHC
molecules thus act as a cell surface vessel for holding and displaying fragments of antigen
so that approaching T cells can engage with this molecular complex via their T-cell
receptors.
The MHC got Its name from the genes in the region, encode proteins that determine
whether a tissue transplanted between two individuals will be accepted or rejected. The
pioneering work of Benacerraf, Dausset, and Snell helped to characterize the functions
controlled by the MHC, specifically, organ transplant fate and the immune responses to
antigen, resulting in the 1980 Nobel Prize in Medicine and Physiology.
History of MHC
Gorer in 1930 was the first to identify the antigens responsible for allograft rejection that
led to the discovery of histocompatible complex (H). He demonstrated two blood group
antigens (antigen 1 and antigen 2) in mice. Antigen 1 was found in all strains of mice, while
antigen 2 was found in certain strains of mice and was responsible for allograft rejection.
This was named H2 antigen and was found to be the major histocompatible antigen. This
antigen was coded for by a closely linked multiallelic cluster of genes called the MHC,
named as H-2 complex.
Histocompatible antigen denotes the cell surface antigens that induce immune responses
to an incompatible host, resulting in allograft rejection. The MHC in humans is known as
Human Leukocyte Antigens (HLA) complex. In humans, these alloantigens are present on
the surface of leukocytes and are called HLA and the set of genes encoding for them is
named the HLA complex. Carbohydrate antigens of erythrocytes (blood groups) and
glycoprotein antigens of cell membranes are the two major transplantation antigens of
humans.
In humans, the HLA complex of genes is located on short arm (p arm) of chromosome 6 (on
chromosome 17 in mice) containing several genes that are critical to immune function.
There are many alleles of MHC genes, and the specific alleles one inherits play a significant
role in susceptibility to disease, including the development of autoimmunity. The
mechanisms by which this family of molecules exerts such a strong influence on the
development of immunity to nearly all types of antigens has become a major theme in
immunology, and has taken the study of the MHC far beyond its origins in the field of
transplantation biology.
, General Properties of MHC Molecules:-
All MHC molecules share certain structural characteristics that are critical for their role in
peptide display and antigen recognition by T lymphocytes.
• Each MHC molecule consists of an extracellular peptide binding cleft, or groove,
followed by immunoglobulin (Ig) like domains and transmembrane and cytoplasmic
domains.
• The polymorphic amino acid residues of MHC molecules are located in and adjacent
to the peptide-binding cleft.
• The non-polymorphic Ig-like domains of MHC molecules contain binding sites for the
T cell molecules CD4 and CD8. CD4 helper T cells recognize class II MHC molecules
displaying peptides, whereas CD8+ T cells recognize class 1 MHC molecules with
bound peptides.
Classification of MHC:-
There are two main classes of MHC molecules:-class 1 and class II. These two molecules are
very similar in their final quaternary structure, although they differ in how they create these
shapes via primary through quaternary protein arrangements. Class I and class II MHC
molecules also differ in terms of which cells express them and in the source of the antigens
they present to T cells.
Differences between Class I & Class II MHC
Class-1 MHC Class-II MHС
Class I molecules are present on all Class II MHC molecules are
nucleated cells in the body and expressed almost exclusively on a
specialize in presenting antigens subset of leukocytes called
that originate from the cytosol. antigen-presenting cells (APCs).
Peptide-binding domain
Peptide-binding domain alpha1/B1
alpha1/alpha2
Peptide binding groove is closed at Peptide binding groove is open at
both ends both ends
General size of bound peptides are General size of bound peptides are
8-10 amino acids 13-18 amino acids
Polypeptide composition is a 45- Polypeptide composition is a 33-
kDa alpha chain and a 12-kDa B2- kDa alpha chain and a 28-kDa ẞ
microglobulin chain
These are presents the antigenic
These are presented to CD8T cells, peptide to CD4 T cells, which then
which recognize and kill cells become activated and go on to
expressing such intracellular stimulate immunity directed
antigens primarily toward destroying.
Extracellular invaders
Activates T cells then initate
Apoptosis of the presenting cell hormonal and cell mediated
immunity
T and B both cells use surface molecules to recognize antigen, they accomplish this in very
different ways. In contrast to antibodies or B-cell receptors, which can recognize an antigen
alone, T-cell receptors only recognize pieces of antigen that are positioned on the surface of
other cells. These antigen pieces are held within the binding groove of a cell surface protein
called the major histocompatibility complex (MHC) molecule, encoded by a cluster of
genes collectively called the MHC locus.
These fragments are generated inside the cell following antigen digestion, and the complex
of the antigenic peptide plus MHC molecule then appears on the cell surface. MHC
molecules thus act as a cell surface vessel for holding and displaying fragments of antigen
so that approaching T cells can engage with this molecular complex via their T-cell
receptors.
The MHC got Its name from the genes in the region, encode proteins that determine
whether a tissue transplanted between two individuals will be accepted or rejected. The
pioneering work of Benacerraf, Dausset, and Snell helped to characterize the functions
controlled by the MHC, specifically, organ transplant fate and the immune responses to
antigen, resulting in the 1980 Nobel Prize in Medicine and Physiology.
History of MHC
Gorer in 1930 was the first to identify the antigens responsible for allograft rejection that
led to the discovery of histocompatible complex (H). He demonstrated two blood group
antigens (antigen 1 and antigen 2) in mice. Antigen 1 was found in all strains of mice, while
antigen 2 was found in certain strains of mice and was responsible for allograft rejection.
This was named H2 antigen and was found to be the major histocompatible antigen. This
antigen was coded for by a closely linked multiallelic cluster of genes called the MHC,
named as H-2 complex.
Histocompatible antigen denotes the cell surface antigens that induce immune responses
to an incompatible host, resulting in allograft rejection. The MHC in humans is known as
Human Leukocyte Antigens (HLA) complex. In humans, these alloantigens are present on
the surface of leukocytes and are called HLA and the set of genes encoding for them is
named the HLA complex. Carbohydrate antigens of erythrocytes (blood groups) and
glycoprotein antigens of cell membranes are the two major transplantation antigens of
humans.
In humans, the HLA complex of genes is located on short arm (p arm) of chromosome 6 (on
chromosome 17 in mice) containing several genes that are critical to immune function.
There are many alleles of MHC genes, and the specific alleles one inherits play a significant
role in susceptibility to disease, including the development of autoimmunity. The
mechanisms by which this family of molecules exerts such a strong influence on the
development of immunity to nearly all types of antigens has become a major theme in
immunology, and has taken the study of the MHC far beyond its origins in the field of
transplantation biology.
, General Properties of MHC Molecules:-
All MHC molecules share certain structural characteristics that are critical for their role in
peptide display and antigen recognition by T lymphocytes.
• Each MHC molecule consists of an extracellular peptide binding cleft, or groove,
followed by immunoglobulin (Ig) like domains and transmembrane and cytoplasmic
domains.
• The polymorphic amino acid residues of MHC molecules are located in and adjacent
to the peptide-binding cleft.
• The non-polymorphic Ig-like domains of MHC molecules contain binding sites for the
T cell molecules CD4 and CD8. CD4 helper T cells recognize class II MHC molecules
displaying peptides, whereas CD8+ T cells recognize class 1 MHC molecules with
bound peptides.
Classification of MHC:-
There are two main classes of MHC molecules:-class 1 and class II. These two molecules are
very similar in their final quaternary structure, although they differ in how they create these
shapes via primary through quaternary protein arrangements. Class I and class II MHC
molecules also differ in terms of which cells express them and in the source of the antigens
they present to T cells.
Differences between Class I & Class II MHC
Class-1 MHC Class-II MHС
Class I molecules are present on all Class II MHC molecules are
nucleated cells in the body and expressed almost exclusively on a
specialize in presenting antigens subset of leukocytes called
that originate from the cytosol. antigen-presenting cells (APCs).
Peptide-binding domain
Peptide-binding domain alpha1/B1
alpha1/alpha2
Peptide binding groove is closed at Peptide binding groove is open at
both ends both ends
General size of bound peptides are General size of bound peptides are
8-10 amino acids 13-18 amino acids
Polypeptide composition is a 45- Polypeptide composition is a 33-
kDa alpha chain and a 12-kDa B2- kDa alpha chain and a 28-kDa ẞ
microglobulin chain
These are presents the antigenic
These are presented to CD8T cells, peptide to CD4 T cells, which then
which recognize and kill cells become activated and go on to
expressing such intracellular stimulate immunity directed
antigens primarily toward destroying.
Extracellular invaders
Activates T cells then initate
Apoptosis of the presenting cell hormonal and cell mediated
immunity
