HAPTENS: HISTORY, FUNCTIONS, CHARACTERISTICS, IMMUNE RESPONSES - BIOLOGY - 2025

A hapten is a non-antigenic, low-molecular-weight non-protein molecule that is capable of eliciting an immune response only when it binds to a protein or carbohydrate “molecular transporter or carrier”. It should be noted that many authors describe it as a “very small antigen”.

An antigenic molecule or antigen is defined in some texts as any substance capable of binding with high specificity to an antibody produced by a B cell or to a receptor on the membrane of a T cell, which are the lymphocytes responsible for humoral and cellular immunity., respectively.

Antigen-antibody complex (Source: Alejandro Porto via Wikimedia Commons)

Antigens can be molecules of any type, such as proteins, metabolites, sugars, lipids and their derivatives, hormones, drugs, nucleic acids, etc.

However, only large macromolecules have the antigenic properties capable of triggering the lymphocyte responses necessary for the production of antibodies.

Any substance foreign to an organism can be considered an antigen, however, the term 'immunogen' is frequently used to refer to those antigens that effectively trigger a response by antibody-producing B lymphocytes.

A hapten is, therefore, a non-immunogenic antigen, which requires its association with a macromolecule to trigger the immune responses characteristic of an immunogen.

Features

Since the immune system is the main "weapon" of defense against infections of different types of pathogens and against any foreign object or substance, among many other things, the body of a human being invests a great amount of effort and energy in its operation.

However, throughout his life a person is regularly exposed to what could be considered as multiple antigens, for which the immune system has the ability to "decide" what type of molecules to respond to and what type of molecules to ignore.

One of the mechanisms that the immune system uses to decide whether or not to respond to a certain antigen is its size. Thus, as discussed above, only "large" molecules such as proteins, phospholipids, complex carbohydrates, and nucleic acids function as true immunogens.

Haptens, since they are very small molecules, unless they are conjugated with some type of macromolecule, do not have immunogenic functions. However, scholars in the branch of medicine known as immunology consider haptens to be immunological "tools."

The reason for the above statement has to do with the fact that some researchers are dedicated to the task of conjugating certain haptens to other larger molecules, which function in their "transport" and render them immunogenic, in order to achieve that a individual produces specific antibodies against a particular hapten.

The molecule resulting from the union between a hapten and a carrier molecule is known as a 'system' or 'hapten-carrier complex' and individuals exposed to this system (truly immunogenic) produce antibodies with the ability to specifically bind to these molecules in their Free form.

Practical utility

So, one of the main functions of hapten-carrier systems is to stimulate the production of antibodies, which are often used in the development of different analytical tests, so they are useful from the point of view of research and diagnosis..

An experimental animal exposed to a hapten coupled with a protein, for example, will produce antibodies against the hapten, against epitopes or antigenic determinants of the carrier molecule, and against sites formed at the junction between the hapten and its transporter.

This property of the hapten-carrier or transporter system is useful for studying the immunological effects of small variations in the structure of an antigen on the specificity of the immune response.

characteristics

Haptens are characterized mainly by their size and by the fact that they are generally non-protein organic molecules. Here is a short list of the main characteristics of these molecules:

- Low molecular weight chemical compounds (less than 5 kDa). They can even be very small functional groups.

Hapten-carrier complex. The hapten in this image is a dinitrophenyl group (Source: MantOs via Wikimedia Commons)

- They are molecules with antigenic specificity, but without immunogenic power or, what is the same, they do not trigger the production of antibodies, but they can be specifically recognized by them in organisms immunized with hapten-carrier complexes.

- Only attached to a “carrier” or “transporter” molecule (from the English Carrier) they acquire immunogenicity as antigens, as they are recognized by the immune system.

- They are univalent from the antigenic point of view, that is, the number of functional antigenic determinants that haptens have, capable of binding an antibody, is only one (unlike a natural antigen, which is polyvalent).

Immune responses associated with haptens and a bit of history

Much of the current knowledge regarding the process of presenting antigens by B lymphocytes, as well as the role of these cells in the development of humoral immune responses, derives from different studies where the antibody response in an immunized organism wanted to be observed. with a hapten-transporter complex.

Karl Landsteiner, between 1920 and 1930, devoted his research to the creation of a chemically defined system to study the binding of individual antibodies, using, for this, animals immunized with hapten-carrier conjugates and comparing their sera with those of other animals. immunized with similar haptens coupled to different molecules.

His comparative experiments were aimed at determining whether there were cross-reactions (that the same antibody recognizes more than one antigen) between the antibodies produced in response to different hapten-carrier complexes, with which he was able to analyze which modifications prevented or allowed these reactions.

Landsteiner's work managed to bring out the specificity of the immune system for small structural variations in the immunogenic determinants of antigens, as well as the great diversity of epitopes that this system has the ability to recognize.

Characteristics of the responses induced by the hapten-carrier complexes

From the studies by Landsteiner and other researchers in the area, some particular characteristics of the immune responses induced by immunization with hapten-carrier protein complexes could be recognized.

- Immune responses require the participation of specific B lymphocytes for each hapten and specific helper T lymphocytes for the protein portion of the transporter.

- Elicitation of a response is only possible when the hapten is physically bound to its carrier protein.

- The antibody-antigen interaction is restricted by the molecules of the class II major histocompatibility complex system.

Later, in the history of immunology it was recognized that these characteristics are also characteristic of antibody responses to any protein antigen.

References

1. Abbas, AK, Lichtman, AH, & Pillai, S. (2014). Cellular and molecular immunology E-book. Elsevier Health Sciences.
2. Actor, JK (2019). Introductory Immunology, 2nd: Basic Concepts for Interdisciplinary Applications. Academic Press.
3. Kennedy, M. (2011). Immunology for dummies-a painless review of basic concepts (Proceedings).
4. Nelson, DL, Lehninger, AL, & Cox, MM (2008). Lehninger principles of biochemistry. Macmillan.
5. Owen, JA, Punt, J., & Stranford, SA (2013). Kuby immunology (p. 692). New York: WH Freeman.