MCB 202: ANTIGEN AND ANTIBODY

ANTIGENS

Antigens are molecules or molecular structures that are foreign to the body and generally induce
an immune reaction through the production of antibodies against them. In simple words, antigens
can be anything that doesn’t belong to the body and are foreign. Antigens are generally of high
molecular weight, and commonly are proteins or polysaccharides, Polypeptides, lipids, nucleic acids, and
many other materials can also function as antigens. Immune responses may also be generated against
smaller substances, called haptens, if these are chemically coupled to a larger carrier protein, such as
bovine serum albumin, keyhole limpet hemocyanin (KLH), or other synthetic matrices. A variety of
molecules such as drugs, simple sugars, amino acids, small peptides, phospholipids, or triglycerides may
function as haptens. Thus, given enough time, just about any foreign substance will be identified by the
immune system and evoke specific antibody production. Even though antigens are usually defined by
the induction of an immune response, all antigens might not induce an immune response. The
antigens that induce a response are called immunogens.

Types of Antigens
Antigens can be grouped into different types based on different factors. Some of the common
classifications are based on the origin of the antigen and its immunogenicity.

1. Types Of Antigen-Based on Their Origin

Antigens can be classified into two groups on the basis of their origin;
a. Exogenous Antigens: Exogenous antigens are the antigens that are originated outside the
body of the host and, thus, are foreign to the host. These antigens might enter the body through
inhalation, ingestion, or injection and then circulate throughout the body via bodily fluids. The
uptake of exogenous antigens is primarily mediated by phagocytosis via Antigen Processing
Cells (APCs) like macrophages, dendritic cells, etc. Many antigens like intracellular viruses
might begin as exogenous antigens and later become endogenous.

b. Endogenous Antigens: Endogenous antigens are antigens that originate within the body of
the host during metabolism or as a result of intracellular viral or bacterial infection. They are
usually the cells of the body or fragments, compounds, or antigenic products of metabolism,
which are usually processed in the macrophages and are later detected by cytotoxic T-cells of the
immune system. Endogenous antigens include antigens that are xenogenic or heterologous,
autologous, and idiotype or allogenic. Endogenous antigens might result in autoimmune diseases
as the host immune system detects its own cells and particles as immunogenic.

c. Autoantigens: Autoantigens are proteins or protein complexes of the host that are attacked by
the host’s immune system, resulting in autoimmune disease. Autoantigens can be deadly to the
host as the body’s own cells should not be targeted by the immune system. The immunological
tolerance to such antigens is lost as a result of genetic and environmental factors.

d. Tumor Antigens (Neoantigens): Tumor antigens or neoantigens are presented by Major

Histocompatibility Complex (MHC) I and II on the surface of tumor cells. These antigens are
produced as a result of a tumor-specific mutation during the malignant transformation of normal
cells. These antigens usually do not induce an immune response as the tumor cells develop ways
to evade antigen presentation and immune defense.

2. Types Of Antigens on The Basis of Immune Response

Antigens can be classified into two distinct groups on the basis of immune response;

a. Complete antigens/ Immunogens: Complete antigens or Immunogens are antigens that elicit
a specific immune response. These antigens can induce an immune response by themselves
without any carrier particles. These are usually proteins, peptides, or polysaccharides with high
molecular weight (greater than 10,000 Da).

b. Incomplete antigens/ Haptens: Incomplete antigens or haptens are antigens that cannot
generate an immune response by themselves. These are usually non-protein substances that
require a carrier molecule to form a complete antigen. Haptens have a low molecular weight
(usually less than 10,000 Da) and fewer antigenic determinant sites. The carrier molecule bonded
to the hapten is considered a non-antigenic component and is a protein or a polysaccharide
molecule.

EPITOPES

The small site on an antigen to which a complementary antibody may specifically bind is called
an epitope or antigenic determinant. This is usually one to six monosaccharides or five to eight
amino acid residues on the surface of the antigen. Because antigen molecules exist in space, the
epitope recognized by an antibody may be dependent upon the presence of a specific three
dimensional antigenic conformation (e.g., a unique site formed by the interaction of two native
protein loops or subunits). This is known as a conformational epitope. The epitope may also
correspond to a simple linear sequence of amino acids and such epitopes are known as linear
epitopes.

ANTIBODIES

An antigen-antibody complex or immunogenic complex is a molecule formed by binding

multiple antigens to antibodies. • The binding of antibody and antigen is determined by the
epitope and paratope present in the antigen and antibody, respectively. The ability of antibodies
to fight against multiple pathogens is due to their ability to distinguish between different
antigens. The interaction between antigens and antibodies is highly specific, and it is determined
by the amino acid sequence in the epitope and paratope of the species. The complex is formed by
an antigen-antibody reaction which is then subject to a number of responses like complement
deposition, opsonization, and phagocytosis. The shape and size of the immune complex are
determined by the ratio of antigen to antibody. The size, in turn, determines the effect of the
immune complex. Antigen-antibody complexes have become an important tool in understanding
the antigen-antibody interaction and determining the basis of molecular recognition between an
antibody and antigens. Immune complexes also play a role in regulating antibody production as
the binding of antigen to cell receptors activates signaling cascade leading to the activation of
antibodies. Even though immune complexes are essential for different immune functions, the
deposition of the immune complex can lead to several autoimmune diseases like arthritis and
scleroderma.

Structure of Antibodies

An antibody, also known as an immunoglobulin is a Y-shaped structure which consists of four

polypeptides — two heavy chains and two light chains. This structure allows antibody molecules
to carry out their dual functions: antigen binding and biological activity mediation, each function
is carried out by different parts of the antibody: fragment antigen-binding (Fab fragment) and
fragment crystallizable region (Fc region).

Fab fragment is a region on an antibody that binds to antigens, it is composed of one constant
and one variable domain of each of the heavy and the light chain. These domains shape the
paratope — the antigen-binding site — at the amino terminal end of the monomer.

Fc region is the tail region of an antibody that interacts with cell surface receptors called Fc
receptors and some proteins of the complement system. This property allows antibodies to
activate the immune system. The Fc regions of immunoglobulin Gs bear a highly conserved
glycosylation site.

Antibodies are heavy (~150 kDa) globular plasma proteins, the basic structure of all antibodies
are the same and consists of four polypeptide chains: two identical heavy chains and two
identical light chains connected by disulfide bonds. Light Chain (L) consists polypeptides of
about 22,000 Da and Heavy Chain (H) consists larger polypeptides of around 50,000 Da or more.
There are five types of Ig heavy chain (in mammal) denoted by the Greek letters: α, δ, ε, γ, and
μ. There are two types of Ig light chain (in mammal), which are called lambda (λ) and kappa (κ).

An antibody is made up of a variable region and a constant region, and the region that changes to
various structures depending on differences in antigens is called the variable region, and the
region that has a constant structure is called the constant region.
TYPES OF ANTIBODIES AND THEIR FUNCTIONS
DIFFERENCES BETWEEN ANTIGENS AND ANTIBODIES

S.N. Characteristics Antigen Antibody

Usually, proteins may also be

1 Molecule Type polysaccharides, lipids or nucleic Proteins
acids.

2 Origin Within the body or externally. Within the body.

Highly variable with different Composed of three main parts:

structural conformations and is -Two light chains
3 Structure
usually composed of different -Two heavy chains
epitopes. -Four polypeptides

Exists in all types of cells;

4 Prevalence mostly found in viruses, bacteria, Only present in some types of cells.
and fungi.

5 Synonyms Immunogens Immunoglobulins

6 Specific binding site Epitope Paratope

Medium; exists due to random Very High; Complex chemical that

7 Complexity
mutations in the cell’s gene. bonds to a very specific Antigen.

Usually from a foreign substance

Naturally produced by the body (B
8 Source (viruses, and bacterial and fungal
lymphocytes or B cells).
toxins).

There are three basic kinds of There are five basic kinds of
9 Kinds antigens (Exogenous, antibodies (IgG, IgM, IgA, IgE, and
Endogenous, and Autoantigens) IgD).

Exogenous antigens: bacteria,

viruses, fungi, etc.
Endogenous antigens: Blood
group antigens, HLA Breast milk, tears, saliva, sweat, and
10 Examples
(Histocompatibility Leukocyte mucus.
antigens), etc.
Autoantigens: Nucleoproteins,
Nucleic acids, etc.