Structure of antibody
Antibodies, also known as immunoglobulins (Ig), are globular proteins belonging to the immunoglobulin family. They consist of four peptide chains, forming a unique structure crucial for their functions. Let’s break down this structure:
Light (L) Chain and Heavy (H) Chain
Each antibody comprises two identical light (L) chain polypeptides, weighing around 22,000 Da, and two identical heavy (H) chains, which are larger, weighing approximately 55,000 Da or more. These chains are bound together by disulfide bonds and various non-covalent interactions, such as salt bridges, hydrogen bonds, and hydrophobic interactions, creating a heterodimer (H-L).
Anatomy of light (L) and heavy (H) chain:
L- chain:
- The L-chain consists of roughly 220 amino acids.
- The N-terminal (amino-terminal) portion of the L-chain, comprising 100-110 amino acids, is known as the variable (V) region, and its sequence varies among different antibodies.
- The remaining amino acids, located at the C-terminal (carboxyl-terminal) end, are relatively constant among antibodies and are referred to as the constant (C) region.
- These constant regions come in two types: Lambda (λ) and Kappa (κ). It’s important to note that a single antibody will contain either two lambda or two kappa chains but not one of each.
- In humans, about 60% of light chains are kappa, while 40% are lambda. In contrast, mice have 95% kappa and 5% lambda light chains.
H-chain:
- The H-chain of antibodies consists of approximately 110 amino acids at the N-terminal region, which exhibit significant variation among different antibodies and is referred to as the Variable (V) region.
- The remaining amino acid sequences of the H-chain are somewhat constant but give rise to five different types of constant (C) heavy chain regions: µ, α, δ, ε, and γ.
- The length of the constant region of the H-chain is 330 amino acids for α, γ, and δ and 440 amino acids for µ and ε.
Antibodies molecules are classified into five class on the basis of constant region of H-chain.
Domain structure of antibody:
- The overall structure of an immunoglobulin molecule is influenced by the primary, secondary, tertiary, and quaternary organization of amino acid molecules:
- Primary Structure: This is the sequence of amino acids that make up the variable and constant regions of the heavy and light chains.
- Secondary Structure: Antibodies fold into a series of beta (β) pleated sheets.
- Tertiary Structure: These folded structures create compact globular domains.
- Quaternary Structure: The globular domains of adjacent heavy and light chains interact to form functional domains that enable the binding of antigens and perform various biological functions.
- In the L-chain, two domains exist—one in the variable region (VL) and the other in the constant region (CL). In the H-chain, a single domain is found in the Variable region (VH). Different classes of antibodies, such as IgA, IgG, and IgD, have varying numbers of domains in their constant regions.
Fab, Fc and Hinge region of antibody:
1. Fab Region (Antigen Binding):
- The amino-terminal (N-terminal) region of the antibody is responsible for antigen binding.
- In an antibody molecule, two Fab regions are found, and they are the parts that actually bind to antigens.
- Hypervariable regions in both the L-chain (VL domain) and H-chain (VH domain) together form the antigen-binding site.
- This site is complementary to the epitope of the antigen and is often referred to as the complementary determining regions (CDRs).
2. Fc Region (Effector Functions):
- The Fc region of immunoglobulins allows for the interaction of immune complexes with other phagocytic cells and complement components.
- The specific biological functions associated with this region are determined by the amino acid sequences of each domain in the constant region.
3. Hinge region:
- The γ, δ, and α heavy chains contain an extended peptide sequence between the CH1 and CH2 domains that is unique and not found in other domains.
- This flexible hinge region, rich in proline residues, allows antibodies like IgG, IgD, and IgA to have flexibility.
- This flexibility is crucial as it enables the Fab region to assume various angles when binding to antigens.
Characteristics of antibodies;
- Antibodies are immunoglobulin (Ig) molecules
- Antibodies are antigen specific and binds to foreign molecules to host.
- They are produced by activated B-cells
- Antibodies are first molecules participating in specific immune response
- They mediate effector function to neutralize or eliminate foreign invaders.
Immunoglobulin classes or Isotypes
Antibody belongs to class of protein called Immunoglobulin (Ig). And classified into 5 classes or isotypes
1. IgG:
- Molecular Weight: 150,000 Da
- H-chain Type: Gamma (53,000 Da)
- IgG is the most abundant class of immunoglobulins in serum, constituting about 80% of total serum immunoglobulins.
- It consists of two gamma (γ) heavy chains and two kappa (κ) or two lambda (λ) light chains.
- IgG has the longest half-life among antibodies, approximately 23 days.
- It is the only antibody that can cross the placenta, providing immunity to the fetus for up to six months after birth.
Biological functions:
- IgG plays a major role in secondary immune responses.
- It readily crosses the placenta, offering natural passive immunity to the fetus.
- IgG can activate complement.
- It mediates opsonization, bacterial immobilization, neutralization of toxins and viruses, and more.
2. IgM:
- Molecular Weight: 900,000 Da
- H-chain Type: Mu (65,000 Da)
- IgM accounts for 5-10% of total serum immunoglobulins, with an average serum concentration of 1.5mg/dl.
- It exists in a pentameric form, with five IgM monomers linked together by disulfide bonds (J-chain).
Biological functions:
- IgM is the first antibody produced in the primary immune response.
- Due to its pentameric form, IgM has higher valency and is highly efficient in agglutination reactions.
- IgM is more effective than IgG in complement activation.
- It plays a crucial role as secretory immunoglobulin due to the J-chain.
3. IgA:
- Molecular Weight: 320,000 Da
- H-chain Type: Alpha (55,000 Da)
- IgA makes up 10-15% of total serum immunoglobulins.
- It is the predominant immunoglobulin in external secretions such as breast milk, saliva, tears, and mucous membranes in the respiratory, genital, and digestive tracts.
- IgA primarily exists as monomeric form but dimeric, trimeric and some tetrameric form are also present.
- IgA in blood occurs in monomeric form whereas those in body secretion occurs in dimeric or multimeric forms.
- Dimeric form of IgA contains J-chain and secretory chain. Secretory chains helps in transcytosis.
- IgA can cross epithelial layer and enter into body secretion. The process of crossing epithelial layer by IgA is known as transcytosis.
- There are two sub-class of IgA ie. IgA1 and IgA2.
Biological functions;
- IgA can cross the epithelial layer and provides local immunity in various body secretions.
- In body secretions, IgA neutralizes viruses and prevents their attachment to host surfaces.
4. IgD:
- Molecular Weight: 180,000 Da
- H-chain Type: Delta (70,000 Da)
- IgD is present in extremely low concentrations, constituting only 0.2% of total serum immunoglobulins.
- IgD together with IgM is the major membrane bound immunoglobulin expressed on mature B-cell.
- There are two sub-classes of IgD (IgD1 and IgD2)
Biological Functions:
- IgD plays a vital role in the maturation and proliferation of B-cells.
5. IgE:
- Molecular weight: 200,000 Da
- H-chain type: epsilon (73,000Da)
- IgE accounts for 0.3% of total serum Immunoglobulin.
- IgE is also known as reagenic antibody due to its involvement in allergic reaction. IgE mediate immediate hypersensitivity reaction and responsible for symptoms like hey fever, asthma, anaphylactic shocks, etc.
- Fc region of IgE binds on blood basophils and tissue mast cells. The cross reaction with antigen to Fc region bound IgE causes degranulation of mast cell and basophils releasing histamine. Histamine is responsible for symptoms of allergy.
Biological functions;
- IgE is known as a reaginic antibody due to its involvement in allergic reactions.
- It mediates immediate hypersensitivity reactions and is responsible for symptoms such as hay fever, asthma, and anaphylactic shocks.
FAQs (Frequently Asked Questions)
- What are antibodies, and what is their role in the immune system?
- Antibodies, also known as immunoglobulins (Ig), are proteins that play a vital role in the immune system. They are produced by activated B-cells and are responsible for recognizing and neutralizing foreign invaders, such as bacteria, viruses, and toxins.
- How do antibodies differ from one another?
- Antibodies differ in their structure and function, leading to different classes or isotypes. These classes, such as IgG, IgM, IgA, IgD, and IgE, have distinct roles in immune responses and provide various forms of protection.
- What is the significance of the different antibody classes?
- The different antibody classes have unique functions. For example, IgG is the most abundant and plays a major role in secondary immune responses, while IgM is the first antibody produced in primary immune responses. IgA provides local immunity in mucous membranes, IgD is involved in B-cell maturation, and IgE is responsible for allergic reactions.
- Can antibodies cross the placenta?
- Yes, IgG is the only antibody that can cross the placenta and provide passive immunity to the fetus, offering protection against certain diseases during the early months of life.
- What is the role of the hinge region in antibodies?
- The hinge region, found in some heavy chains of antibodies, is flexible and allows the Fab regions to assume various angles when binding to antigens. This flexibility is crucial for effective antigen recognition and binding.
Structure of Antigens