Antigenic specificity : Species Specificity and Autospecificity

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The antigenic specificity of the antigen is determined by antigenic determinants or epitopes.

What is an Epitope?


The immunologically active region of an immunogen that binds to antigen-specific membrane receptors on lymphocytes or secreted antibodies is referred to as an epitope. The interaction between immune cells and antigens occurs on multiple levels, and the complexity of any antigen is mirrored by its epitope.

Epitopes are classified into two types: B-cell epitopes and T-cell epitopes.

  • B-cell epitopes

B-cell epitopes are antigenic determinants that B cells recognize. Only when the antigen molecule is in its native state can the B-cell epitope combine with its receptor. The antigen and antibody molecules’ complementary surfaces appear to be relatively flat. Smaller molecules frequently fit snugly within a depression or groove in the antibody molecule’s antigen-binding site.

The B-cell epitope is approximately six or seven sugar residues or amino acids in length. B-cell epitopes are hydrophilic in nature and are frequently found at protein bends. They are also frequently found in protein regions with higher mobility, which may allow an epitope to shift just a little to fit into an almost-right site.

  • T-cell epitopes

T cells recognize protein amino acids but not polysaccharide or nucleic acid antigens. This is why polysaccharides are classified as T-independent antigens while proteins are classified as T-dependent antigens. The antigenic determinants recognized by T cells are determined by the primary sequence of amino acids in proteins. T cells do not recognize free peptides, but they do recognize the complex of MHC molecules and peptide. As a result, for a T-cell response to be MHC restricted, it must recognize both the antigenic determinant and the MHC.

T-cell epitopes, also known as antigenic determinants, are typically 8–15 amino acid long. The antigenic determinants are restricted to antigen components that can bind to MHC molecules. Because MHC molecules are subject to genetic variation, there may be differences in T-cell responses to the same stimulus among individuals. Each MHC molecule can bind a number of peptides, but not all of them. As a result, for a peptide to be immunogenic in a specific individual, that individual must have MHC molecules capable of binding to it.

Species Specificity

Certain species-specific antigens are present in the tissues of all individuals in a species. However, there is some cross-reaction between antigens from related species. The species specificity demonstrates the phylogenetic relationship. The phylogenetic relationship is useful in the following situations:

  • The study of the evolutionary relationships between species.
  • In forensic medicine, species identification from blood and seminal stains.


The presence of isoantigens or histocompatibility antigens determines isospecificity.


Isoantigens are antigens that are present in some but not all members of a species. A species can be classified based on the presence of specific isoantigens in its members. These are determined by genetics. Human erythrocyte antigens, which are used to classify individuals into different blood groups, are the best examples of isoantigens in humans. The blood groups are crucial in the following situations:

  • Blood and blood product transfusion
  • During pregnancy, isoimmunization is recommended.
  • Providing important evidence in paternity disputes, with the results supplemented by more recent DNA fingerprinting tests.

Histocompatibility Antigens

Histocompatibility antigens are cellular determinants that are unique to each individual in a species. These antigens bind to the plasma membrane of tissue cells. The major histocompatibility antigen that determines homograft rejection is human leukocyte antigen (HLA). As a result, HLA typing is absolutely necessary before performing tissue or organ transplantation from one individual to another.


In general, self-antigens are not antigenic. However, sequestrated antigens (such as eye lens protein and sperm) are exceptions because they are not recognized as selfantigens. This is due to the immune system never encountering corneal tissue or sperm during the development of tolerance to self-antigens. As a result, if these tissues are accidentally or experimentally released into the blood or tissues, they become immunogenic.

Organ Specificity

Organ-specific antigens are antigens that are specific to a specific organ or tissue. The antigen specificity of these antigens found in the brain, kidney, and lens tissues of different animal species is the same. Brain-specific antigens, which are shared by human and sheep brains, are one such example. When antirabies vaccines made from sheep brain are administered, they may cause an immune response in some humans, causing damage to the recipient’s neural tissues. Some people may develop neuroparalytic complications as a result of this.

Heterophile Specificity

Heterophile specificity is determined by the presence of heterophile antigens. The same or closely related antigens, which are sometimes found in tissues from different biological species, classes, or kingdoms, are referred to as heterophile antigens. Antibodies against heterophile antigens produced by one of the species cross-react with antigens from other species.This property is used in the diagnosis of many infectious diseases. Serological tests that use such heterophile antigens include the Weil–Felix reaction, the Paul-Bunnell test, and cold agglutination tests.


Haptens are antigenic but not immunogenic small organic molecules. They are not immunogenic because they are incapable of activating helper T cells. The inability of hapten to bind to MHC proteins is due to their inability to bind because they are not proteins and only proteins can be presented by MHC proteins. Furthermore, because haptens are univalent, they cannot activate B cells on their own.

Haptens, on the other hand, can activate B cells when covalently bound to a “carrier” protein. They form an immunogenic hapten–carrier conjugate when bound with a carrier molecule. The haptens combine with an IgM receptor on the B cells during this process, and the hapten–carrier protein complex is internalized. To helper T cells, a peptide of the carrier protein is presented in conjunction with class II MHC protein. Helper T cells that have been activated then produce interleukins, which stimulate B cells to produce antibodies against hapten.

Hapten–carrier conjugate.
Hapten–carrier conjugate.

Animals immunized with such a conjugate produce antibodies that recognize

(a) the hapten determinant

(b) unaltered epitopes on the carrier protein

(c) new epitopes formed by combining parts of the hapten and carrier.

The hapten–carrier molecule is, in fact, bound to surface immunoglobulins on B cells via hapten epitopes. These B and TH cells then take in the hapten–carrier molecule, process it, and present pieces of the carrier. The formation of hapten–carrier conjugates in the body is the basis for the development of allergic responses to drugs such as penicillin.


Superantigens are a type of molecule that can interact in an unspecific manner with APCs and T lymphocytes. The superantigens interact with MHC class II molecules of the APC and the Vb domain of the T-lymphocyte receptor in different ways. This interaction activates a greater number of T cells (10%) than conventional antigens (1%), resulting in massive cytokine expression and immunomodulation. Superantigens include staphylococcal enterotoxins, toxic shock syndrome toxin, exfoliative toxins, and viral proteins.


Textbook of Microbiology and Immunology, 2 Subhash Chandra Parija P.107-109

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About the Author: Labweeks

KEUMENI DEFFE Arthur luciano is a medical laboratory technologist, community health advocate and currently a master student in tropical medicine and infectious disease.

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