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Paper No.: 10 Immunology

Module : 2 Antigen recognition by immune cells – Adaptive immunity, Antibody

Development Team

Principal Investigator: Prof. Neeta Sehgal Head, Department of Zoology, University of Delhi

Paper Coordinator: Prof. Anju Srivastava Department of Zoology, University of Delhi

Content Writer: Dr. Rajni Arora Swami Shraddhanand College, University of Delhi

Content Reviewer: Prof. Sukhmahendra Singh Banaras Hindu University

Immunology ZOOLOGY Antigen recognition by immune cells – Adaptive immunity, Antibody

Description of Module

Subject Name ZOOLOGY

Paper Name Immunology; Zool 010

Module Name/Title Antigen recognition by immune cells – Adaptive immunity, Antibody

Module Id 2; Antigen recognition by immune cells

Keywords Immunity, adaptive, antibody, antigen, epitope, light chain, heavy chain, B lymphocyte, T lymphocyte, humoral immunity, isotypes, effector function

Contents

1. Learning Outcomes 2. Introduction 3. Adaptive Immunity 4. Antibody 4.1. Unique features of tool of humoral immunity: antibody 4.2. Important discoveries /research work in the field of antibody 4.3. Structure of antibody: light chain, heavy chain, J chain, Hinge region, disulphide bond, carbohydrate group 4.3.1 Experiment of Tiselius and Kabat 4.3.2 Experiment of Rodney Porter and G. M. Edelmann 4.4 Structure of antibody (Light chains, heavy chains, J chain, hinge region, carbohyrate group, disulphide bond) 5. Types of antibody 5.1. IgG 5.2. IgM 5.3. IgA 5.4. IgE 5.5. IgD 6. Functions of Antibody 6.1. Opsonisation 6.2. Complement activation 6.3. Antibody mediated cell cytotoxicity ADCC 6.4. Transcytosis 6.5. Passive immunity 7. Summary

Immunology ZOOLOGY Antigen recognition by immune cells – Adaptive immunity, Antibody

1. Learning Outcomes

The study of the chapter will help in understanding the following:

 What is adaptive immunity?  How is the structure of antibody deduced?  Why is it an important component of adaptive immunity?  How it is a component of antigen recognition unit?  What are the various isotypes of antibody?  How do the antibodies function to combat the pathogen?

2. Introduction

The chapter focuses on the biology of antibody which is an important effector molecule of the humoral adaptive immunity. Antibodies or immunoglobulins which were earlier called magic bullets are released in millions on activation of B lymphocytes. The study of structural detail of the molecule is important to understand its function which is of great help to customize and manipulate it commercially for various diagnostic and therapeutic uses. The important attributes of specificity and diversity gives it the convenience to act at the strategic locations targeting variety of antigens entering through different routes. The antibody is not only released in the body fluids but is also located on the B cells as membrane receptors where it is a part of antigen recognition unit of B cell. The magic of the antibody is clarified once we analyse its role as a static molecule on the B cells (mIg) and a mobile effector molecule in blood and other secretions.

3. Adaptive Immunity

The adaptive immunity is given by the activation of two types of cells in the blood that is B and T lymphocytes. These specialized cells are named on the basis of their immunological training in the Bone marrow or Thymus respectively. Adaptive immunity is also called acquired immunity as it starts after the exogenous or endogenous antigen enters and infects the body. B cell attacks the exogenous (outside) antigen and T cell is deputed for endogenous (inside) antigen (Figure 1). It starts a few days after infection as it gives the first chance to the innate mechanisms to provide the first line of defense. Adaptive immunity has three important roles of recognizing, eliminating and remembering the pathogen by producing few memory cells (Figure 2). It also has the power of giving immunity specific to the antigen due to presence of different receptors that is BCR and TCR located on B and T cells. It is called acquired immunity as it is a specialized defense mechanism which adapts on acquiring infection. The existence of two different types of lymphocytes that is B and T lymphocytes was first reported by J. A. Pierre Miller and G. F. Mitchell in 1966. Both the lymphocytes work efficiently in a co-operative manner to give humoral and cell mediated immunity. The response given by B cells is called humoral and the response given by T lymphocytes is called cell mediated. There are two subpopulations of T

cells called T helper or Th and T cytotoxic cells or Tc where Th cells decides what is to be activated that is cell mediated immunity or humoral immunity. There is another subpopulation of T cells called T-

suppressor cells (Ts). They are the negative regulators of immunity and suppress the immune response if 3

Immunology ZOOLOGY Antigen recognition by immune cells – Adaptive immunity, Antibody

there is over reaction in the body or reaction for self proteins. They are thus called immunoregulator cells. The mature B or T cell which waits for encounter with the antigen for the first time is called Naïve lymphocyte. Adaptive immunity differs from innate immunity in its antigenic specificity and presence of memory cells. The memory cell membrane has the same receptors as the activated lymphocyte but recognizes the antigen faster, if, it dares to enter the body again.

Figure 1: B and T cells

Figure 2: Showing Naive B cell and memory B cell Source: www. en.wikipedia.org

4. Antibody

All the vertebrates are gifted with the ability to form large sized multifunctional glycoprotein called antibody for giving the protection against the invading antigens. It is released in the blood and other body fluids like milk, saliva, tears etc. because of which this type of immune response is called humoral immunity (in Latin humor means fluid). The term antibody has originated from the German word Antikorper. It was first coined by Von Behring and Kitasato in 1890 to describe an agent in blood that was capable of passively transferring the immunity. They suggested that there exist an entity which could act against the (anti) offending toxin. The antibodies may be located on the membranes of the B cells or they may be secreted. The membrane bound antibody (mIg) acts as a receptor on the B cells (BCR) for Ag recognition and the secreted form is for neutralization, clumping, precipitation and 4

Immunology ZOOLOGY Antigen recognition by immune cells – Adaptive immunity, Antibody

agglutination etc. of Ag. The antibody present on the B cell makes it antigen specific (Figure 3) by recognizing epitopes present on the antigen and activating the same cell after the signal is transduced. The B cell is also an antigen presenting cell where it first endocytose the antigen and display it with the membrane molecule MHCII. It is then activated by cytokines of Th cells. The B cell once activated proliferates and produces clones of antigen specific B cells which finally changes into the antibody secreting plasma cells (Figure 4). The antibodies try to inactivate, neutralize, agglutinate, precipitate and clump the microbes so that they may not multiply and colonise in the organs they invade.

Figure 3: Antibody showing antigen specificity Source: Wikimedia.Org

. Figure 4: Activated B cell Source: www Wikipedia.org 5

Immunology ZOOLOGY Antigen recognition by immune cells – Adaptive immunity, Antibody

4.1. Unique features of tool of humoral immunity: antibody

 Antibody is an immunoglobulin.  Antibody is an adaptor molecule as it is a bridge between antigen and effector molecule.  Antibody is a glycoprotein.  Antibody is a heterodimer.  Antibody is an effector molecule.  Antibody is specific to a single epitope  Antibody in the serum is heterogenous.  Antibody can act as antigen. Antibody raised against antibody is called anti-antibody.  Antibody is of five types varying in the effector functions.  Antibody can be monomeric or polymeric.  Antibody is monoclonal and polyclonal.  Antibody is a flexible molecule.  Antibody is of two types: Membrane bound and Secretory.  Membrane antibody is for antigen recognition as BCR.

4.2. Important discoveries/ research in the study of antibodies

 P. Ehrlich, 1900: Antibodies are magic bullets to target human disease and gave selection theory of antigen and antibody.  E. Von Behring: Serum antitoxins. Got Nobel Prize in 1901  Arne Tiselius and Elvin Kabat: Antibodies are serum proteins/immunoglobulins. Discovered in 1939  Karl Landsteiner 1940: Demonstrated that antibodies are specific in their recognition by using hapten.  Eisen and Karush in 1940 showed that antibody is divalent.  L. Pauling and D. Pressman 1945 suggested that there are pockets in antibodies where antigen binds and the interaction between the two is non covalent.  Rodney Porter and G. Edelman gave chemical structure of antibody. Got Nobel Prize in1972.  G. Edelman in 1970 showed that heavy chains are involved in effector function of antibody.  Wu and Kabat in 1970 identified the hyper variable region on the antibody.  Cesar Milstein, George Kohler, Neil Jerne: Monoclonal antibody. Got Nobel Prize in 1984  Susuma Tonegawa: gene rearrangement in antibody production. Got Nobel Prize in 1987.  Timosi T.B: Biological function of Ig A  D. Rowe and J. Fahey: Biological function of Ig D  O. Prausnitz and H. Kustner: PK reaction to study allergy (IgE).

Immunology ZOOLOGY Antigen recognition by immune cells – Adaptive immunity, Antibody

4.3. Landmark experiments to study the anatomy of antibody

4.3.1. Experiment of Tiselius and Kabat

A. Tiselius and E.A. Kabat in 1939 worked on immunized rabbits by using the technique of electrophoresis. By this technique the proteins on the gel when subjected to the electric current are separated according to their size (Figure 5). They immunised the rabbit with the antigen ovalbumin. Ovalbumin (OVA) a storage protein (45KDa) of Fowl egg is a good immunogen for the mammals due to its large size and easy availability for immunization. They took the serum of the immunized rabbit and divided it into two parts before electrophoresis. Out of the two parts which were electrophoresed, one part was mixed with ovalbumin before electrophoresis. The second part of serum which was not mixed with ovalbumin showed four peaks corresponding to albumin and α, β, γ globulin, but in the serum mixed with ovalbumin the gamma peak in the graph was absent. They concluded that the antibodies are in the gamma globulins fraction and hence named gamma globulin or immuno globulins. With the advancement in electrophoretic technology, it is known that IgG the major antibody exist in gamma fraction but alpha and beta globulins also contain other classes of antibody.

Figure 5: Electrophoretic separation of serum proteins to show the presence of immunoglobulins

4.3.2. Experiment of Rodney Porter and G. M. Edelmann

The insight into the structure of antibody was given by Rodney Porter and Gerald M Edelmann for which they shared the Nobel Prize in Physiology in 1972, though they worked independently on the molecular structure of the antibody (presentation speech). The large protein immunoglobulin was broken using different enzymes like pepsin and papain (by R. Porter) and reducing agents like Mercaptoethanol (2ME), (by G.M. Edelmann). The results were then compiled to deduce the Y shaped structure of antibody. Pepsin cleaved the immunoglobulin at site of aromatic aminoacids like tyrosine, tryptophan and phenyalanine resulting in two Fab and one Fc parts but the cleavage site of papain (enzyme obtained from papaya latex) is at the cysteine residues. The cleavage product of papain was a single piece with two Fab components. The Fc fragment was digested by the enzyme

Immunology ZOOLOGY Antigen recognition by immune cells – Adaptive immunity, Antibody

completely. Mercaptoethanol broke the secondary and tertiary structure of the protein by reducing the disulphide bonds thus releasing the polypeptide chains of two different sizes called as light and heavy chains (Figure 6). The large heavy chain was of 55 KDa but the light chain was of 22KDa. A variety of antibody types was listed by deciphering the amino acid sequences. The amino acid sequence of the antibody was studied using cancerous plasma cell called myeloma cells. Variation in the amino acid sequence of the light chains was later obtained using Bence jones (BJ) proteins. Bence Jones proteins are immunoglobin light chains (22-24KDa) produced by the neoplastic plasma cells. They clumped when heated at high temperature. Based on the studies of BJ proteins, there are two types of light chains, called kappa and lambda differing in the constituition of constant regions. The heavy chains and the light chains both have variable and constant regions. The constant regions of heavy chains are of five types determining the five classes of antibodies as IgM, IgG, IgD, IgE and IgA.

Figure 6: Effect of proteolytic enzymes and mercaptoethanol on antibody

Immunology ZOOLOGY Antigen recognition by immune cells – Adaptive immunity, Antibody

4.4. Structure of antibody (Light chains, heavy chains, J chain, hinge region, carbohydrate group, disulphide bond)

Light chain and heavy chain

The antibodies are proteins made of four polypeptide chains, the two large sized of 55KDa each are called heavy chains and the small sized polypeptide of 25KDa called light chains (Figure 7). The two different light and heavy chains organize to form a Y shaped three dimensional structure of the antibody due to intra and inter disulphide bonds and other noncovalent interactions. The protein nature of Ab also contributes to the two functionally different N and C-terminals with specific roles. N-terminal shows variability in amino acid sequence compared to C-terminal of polypeptide. The region of the heavy and

light chain showing amino acid variation in each molecule is denoted as VL and VH and constant region

as CH and CL

Figure 7: Antibody structure Source: Commons.wikimedia.org

The intrachain disulphide bonds at a regular interval of 110 aminoacids result in converting the peptide chain in to a compact globular domain. Each light chain consists of a single constant domain

called as CL, whereas, the heavy chain has two or three constant domains called as CH1, CH1 and CH3. (Figure 8 and 9)

Figure 8: Antibody domain structure Source: Commons.wikipedia.org

Immunology ZOOLOGY Antigen recognition by immune cells – Adaptive immunity, Antibody

Figure 9: Domains making heavy and light chain. Yellow and green are the light chains and blue and red are the heavy chains Source: www.wikipedia.org

The study of secondary and tertiary structure of Ab shows all the immunoglobulin domains have β pleated sheets, each consisting of three or four strands of anti-parallel polypeptides connected by loops of variable length. The two β pleated sheets are connected by the conserved disulphide bonds. The characteristic protein motif found in immunoglobulins is called immunoglobulin fold. N – terminal variation in composition of heavy and light chain facilitates the execution of humoral response to a variety of antigens. Within the variable domains of light and heavy chains there are short amino acid sequences with exceptional variability at three locations called hypervariable regions. They are also called complementarity determining region or CDR as they are the regions which protrude out to form the peptide loops giving a shape complementary to the shape of the antigenic determinant/epitope. There are three CDRs named CDR1, CDR2 and CDR3 which cluster to give the shape to the antigen binding site of antibody also termed as paratope. Ag-ab interaction occurs at epitope of the antigen and paratope site of antibody. The rest of the variable region is called the framework region as it provides a scaffold to hold the hypervariable regions in place.

There are two types of the light chains in the monomer of antibody called lambda (λ) and kappa (κ). The names lambda and kappa represent the first letter in Greek of the two scientists Korngold and Lipari who first discovered them. Combination of both types of light chains is present in each individual but the percentage composition may vary in different species. There are five different types of heavy chains named as α, µ, γ, δ, ε based on the difference in the constant region of the heavy chain. The antibody with five different types of the heavy chains exist in an individual and are further called classes/isotypes. Each isotype has not only a distinct physical and biological property but differs in its effector functions. The antibody with α chain is called antibody A, with μ chain is called antibody M and accordingly antibody G, D and E. The subisotypes of the heavy chains also exist due to the small amino acid variation in the isotypes. α1, α2 are the subisotypes of antibody A and γ1, γ2, γ3 and γ4 are the subisotypes of antibody G. The different isotypes and its subtypes vary in performing effector functions like opsonisation, complement activation, neonatal immunity etc. Most of the effector functions are mediated by the C- terminal of the heavy chain of the antibody as it binds with the receptors (FcR) on the cells like NK, mast cells, phagocytes etc.

The antibody is also classified as monomeric and polymeric. Monomeric antibody has two binding sites for an antigen but the multimeric antibody has more than two binding sites. This interaction of

Immunology ZOOLOGY Antigen recognition by immune cells – Adaptive immunity, Antibody

antibody with the antigen is possible because of flexibility in the two arms of the antibody by the presence of the hinge region specially in the IgG, IgD and IgE. The antibody which is specific for a single epitope is called monoclonal antibody. The human serum contains a cocktail of antibodies specific for various antigens and is called polyclonal serum. The monoclonal antibodies are prepared in vitro by hybridoma technology. They are used as therapeutic and diagnostic agents.

Source www.wikipedia.org Value addition: Antibodies are used in therapeutics to treat various diseases

Hinge region: The hinge region is located between CH1 and CH2 domains of the antibody (Fig 10). It is mainly made of two types of amino acids that is proline and cystine which are vulnerable to the attack by the proteolytic enzyme like papain. The proline amino acids provides the flexibility to the arms of Ab but the cystine amino acid helps in forming the interchain disulphide bonds. The hinge allows the two antigen binding Fab region of each antibody molecule to operate independently so that it can bind antigen epitopes which are distantly separated. Though the arms are flexible but this flexibility also hinders in saturating all the binding sites of the multimeric antibody. IgG3 has the longest hinge region amongst the subtypes of IgG. The hinge region varies in length from 10 to 60 amino acids approximately.

J Chain: These are small proteins coded by different genes which connect the units of the polymeric immunoglobulin. It is a joining chain with a molecular weight of approximately 15KDa and is linked by the disulphide bond to the C- terminal of the heavy chains.

Disulphide bond: Heterodimeric antibody has intra and interchain disulphide bonds between the peptide chains which give stability to its three dimensional Y shaped molecular structure.

Carbohydrate group: The immunoglobulins are glycosylated which means the carbohydrate moiety is attached to it which is important for the passage of the antibody through the biological membranes and placental barriers. All the isotypes have a different half life. The shortest half life is of IgE that is of two days, IGA of three days, IgM of four days and IgG has longest half life of 21-28 days. The 11

Immunology ZOOLOGY Antigen recognition by immune cells – Adaptive immunity, Antibody

long life of IgG is attributed to the FcRn (neonatal Fc receptor) which protects it from lysosomal degradation for a long time.

Figure 10: Structure of Antibody (modified)

5. Types of Antibody

The five different types of antibodies (IgG, IgM, IgA, IgE, IgD) perform different biological functions and each type is important so as to kill or inactivate the pathogen entering through various routes in the body (Figure 12 and Table 1).

5.1. IgG

The IgG is monomeric antibody having the highest concentration in the serum. It constitutes about 80% of the total serum concentration.It is a good complement activator, can cross placenta and gives the passive immunity to the foetus. It also mediates the opsonization process by the macrophages and the neutrophils. Based on the minor aminoacid differences in the heavy chain, it has been divided in four subclasses namely IgG1, IgG2, IgG3, and IgG4. There is difference in the number of disulphide bonds and the size of the hinge region in the subclasses of the isotype IgG. Out of the four subtypes, IgG1 is best in giving passive immunity to the foetus and in mediating the process of opsonization. IgG3 is the best activator of complement. Its concentration is less in the primary immune response but increases in the secondary immune response.

5.2. IgM

It is the antibody present on both the cell membrane and in secretions. The membrane bound antibody is monomeric but the secretory form is pentameric. Though it can bind with ten epitopes but there is steric hindrance as a result it can interact with the maximum of six or seven epitopes. It is existing in the serum with only 5-10% of the total concentration and a very less amount exist in the mucosal secretions. It is the antibody for the primary response as it appears first in response to the infection. The pentameric

Immunology ZOOLOGY Antigen recognition by immune cells – Adaptive immunity, Antibody

secretory form of IgM helps to attack the pathogen quickly. It can not cross the placental barrier due to its polymeric nature. It is the first antibody to be produced by the neonate. The five monomers of the antibody are linked to each other by the joining chain or J chain. The J chain is synthesized in the plasma cell. The J chain also helps in transport of the antibody across the epithelial layers as mucosal secretion. It is the best complement activator and forms big aggregates of agglutination. It is also important to know that the IgM also include Isohaemagglutinins which are the naturally occurring antibodies against the red blood cell antigens and thus determine the ABO blood group system (Figure 11). These antibodies might have originated as a result of some bacteria entering through the various routes as discussed earlier. These bacteria had antigenic determinants similar to the oligosaccharide antigen of the ABO Blood group. Thus without the immunization of individuals, anti-A or anti-B or both may be present in the blood as given in the Fig11. The pentameric nature of IgM does not allow it to cross the placenta so incompatibility of ABO is not dangerous to mother and foetus.

Figure 11: ABO Blood group Source: www. commons wikimedia.org

5.3. IgA

It is the type of antibody which exist in the serum and in the mucosal secretions of the respiratory, gastrointestinal and urinogenital tract. It is dimeric, trimeric or tetrameric in its secretory form. It is mostly transported as dimeric form. It is also assisted by the J chain for the polymerization and for the transport to the mucosal surface. It is important as it coats the antigen and prevents its attachment to the mucosal layers. Thus for protection against local infections, routes of immunizations causing local production of IgA is better than those producing antibody in serum. As the complement receptors are absent on IgA molecule so it is not a complement activator.

5.4. IgE

It is present in very less concentration in the serum but, is biologically very potent to induce hypersenstive reaction against an allergen. It is named antibody E because of the antigen E present on 13

Immunology ZOOLOGY Antigen recognition by immune cells – Adaptive immunity, Antibody

the ragweed pollen. The presence of this antibody was first detected by Prausnitz and Kusner in 1921 and the reaction is also called PK reaction. It binds to the Fc receptors present on the membranes of basophils and mast cells .The cross linking of the allergen with the antibody bound to Fc receptors on the same cell results in giving the signal for the degranulation of the pharmacologically active reagents which cause a reaction like wheal and flare or hives etc.

5.5. IgD

It is present as membrane bound antibody on the mature B cells. It acts as a receptor on B cells so called BCR. Its biological function is not very clear. It is less than 5% of total serum immunoglobins.

Table 1: Types of antibody and their properties

Source: www.wikimedia.org

Immunology ZOOLOGY Antigen recognition by immune cells – Adaptive immunity, Antibody

IgM , IgD

Figure 12: Types of antibody showing secretory and membrane bound Source: Spot Pcc.Edu modified diag

6. Functions of Antibody

The two different components of Ab that is the Fab and Fc are for epitope –paratope interaction and effector function respectively. The various functions of antibody are:

6.1. Opsonization

It is the coating of the antibody on the surface of the antigen due to the epitope - paratope interaction which makes the antigen more vulnerable to attack by both the phagocytic and nonphagocytic cells (Figure 13 and 14). The phagocytic cells like macrophages and neutrophils and some non-phagocytic cells have the receptors

(FcR) for binding with the FC of antibody. This interaction results in initiating the signal transduction pathway for the different mechanisms of the phagocytic activity for the secured killing of the pathogen.

Figure 13: Opsonisation Figure 14: Opsonisation (animated form) Source: www.en.wikipedia.org

Immunology ZOOLOGY Antigen recognition by immune cells – Adaptive immunity, Antibody

6.2. Complement activation

Complements are the set of serum proteins which when activated make perforations in membrane of pathogen and finally kill it (Figure 15).

Figure 15: Complement activation Source: commons Wikimedia.org

6.3. Antibody mediated cell cytotoxicity ADCC

The natural killer cells (NK) are activated for its cytotoxic function by the antigen- antibody interactions as these cells have the Fc receptors on their membranes. (Figure 16)

Figure 16: ADCC Source: www.en.wikipedia.org

Immunology ZOOLOGY Antigen recognition by immune cells – Adaptive immunity, Antibody

6.4. Transcytosis

The Fc component of Ab assists in transfer of the antibody from the epithelial layer to the mucosal surface of the gastrointestinal, respiratory and the urogenital tracts. It binds with the polyIg receptor on the basolateral side of the epithelial cell which is endocytosed and then excreted in the mucosal surface.

6.5. Passive immunity

The growing embryo in the mother’s body that is fetus is protected by passive immunity as IgG is selectively transported across the placenta mediated by neonatal Fc receptors (FcRn). Maternal immunogen is also transferred to the offspring through the transport of IgG across the gastrointestinal tract.

Ag and Ab interactions involve four types of noncovalent interactions making it a reversible reaction (Figure 17). Antibodies can also become potent immunogen and can induce immune response. Based on the difference in light and heavy chains they are classified as isotypes, allotypes and idiotypes. Isotypes are due to difference in the constant regions of heavy chains and are species specific. The allotypes are due to the allelic difference in the genes resulting in variation in the amino acids in the constant domains of the heavy and light chains. The idiotypes may arise due to the difference in the aminoacids in the variable portions of the heavy and light chains

Figure 17: Showing Ag-Ab forces (modified)

Immunology ZOOLOGY Antigen recognition by immune cells – Adaptive immunity, Antibody

Figure 18: Affinity and Avidity: Pentameric antibody showing avidity

The binding strength of a single epitope and paratope is called affinity but the total strength of interaction of multiple epitopes and multivalent antibody is called avidity. Since the antibody can bind 2-10 epitopes of an antigen the total strength is more than affinity of single antigen and antibody (Figure 18).

Some hot spots in the antibody research are designer Ab, chimaeric Ab, Antibody as immunosensor etc

Source: www.genscript.com

Immunology ZOOLOGY Antigen recognition by immune cells – Adaptive immunity, Antibody

7. Summary

 Antibody is the important effector molecule of the adaptive immune system.  It is a Y shaped glycoprotein with Fab and Fc components.  It has diversity as it is specific to variety of antigens which are encountered in the blood and other body fluids.  It is both membrane bound and secretory.  Membrane bound antibody is for recognition of antigen and is part of recognition unit called BCR.  Each component of Ab that is, light and heavy chain, hinge region, disulphide bonds, J chain and carbohydrate group gives it special properties and makes it a versatile molecule.  It has five isotypes as IgA, IgM, IgG, IgD and IgE.  Each type functions at strategic locations of the body.  The various effector functions like ADCC, complement activation, opsonisation etc aim to target the antigen and differ in isotype and sub isotype.  The Ag- Ab interactions are noncovalent and occur at the epitope of antigen and paratope of antibody.

Immunology ZOOLOGY Antigen recognition by immune cells – Adaptive immunity, Antibody