Cross-reactivity

Overview

The ability of a single antibody to recognize multiple structurally similar epitopes is an important immune defense strategy that enables the host to efficiently defend against many potentially threatening pathogens. However, cross-reactivity also elicits allergy symptoms against related allergens. It is increasingly important to understand the principles of cross-reactivity, as antibodies are actively being developed as therapeutic modalities for diverse diseases, including cancer.

Structurally Similar Epitopes May Be Found on Different Antigens

Antibodies can initiate an immune response by binding to specific structures on the surface of pathogens or other foreign elements. By definition, anything that is bound by an antibody, and subsequently elicits an immune response, is called an antigen. Often, antigens are proteins on the surface of viruses, bacteria, fungi, and protozoan invaders. The specific sequence of amino acids that is recognized by the antibody is called an epitope. Most epitopes are only 5-6 amino acids long. As such, a single antigen may present several distinct epitopes. Cross-reactivity occurs when two distinct epitopes are structurally similar, and hence are recognized by the same antibody.

Cross-Reactivity Facilitates Immunity against Related Pathogen Strains

A major benefit of antibody cross-reactivity is that it provides cross-protective immunity to related pathogens. When a circulating antibody recognizes a viral or bacterial pathogen that it has encountered previously, it mounts a rapid immune response and targets the pathogen for destruction. This process is called immunological memory. Cross-reactivity allows the same antibody to recognize and provoke a similarly robust immune response to a closely related but previously unencountered antigen. In this way, a less specific antibody provides broad-spectrum immunity despite antigenic variation in pathogens.

Cross-Reactivity Can Increase the Number of Allergens

An allergy occurs when antibodies recognize antigens from benign sources (e.g., foods, plants, animals) as invading pathogens and inappropriately mount an immune response against them. In the case of an allergy, the antigen is called an allergen. Antibody cross-reactivity can, unfortunately, increase the number of allergens that an allergic person reacts to. While the initial allergic reaction was induced against a specific allergen (e.g., walnut), cross-reactivity lets the immune system act against additional, structurally similar allergens (e.g., pecan). These allergens may be similar in nature, such as shrimp and lobster, or unrelated, such as banana and latex. Yet they present structurally similar epitopes and therefore induce an immune response that is mediated by the same antibody.

Vaccination with a Cross-Reactive Antibody May Curb Several Deadly Forms of Ebola

Ebola is an often deadly disease that is caused by the Ebola virus. Four of the six Ebola species are pathogenic to humans. The virus spreads easily by transmission of body fluids and causes local outbreaks. Only in recent years have researchers developed a vaccine against the Zaire strain of the Ebola virus. The vaccine successfully protected health workers in an acute Ebola outbreak in the Democratic Republic of the Congo in 2018. The vaccine needs to undergo additional testing to demonstrate its safety but is a hopeful candidate for preventing the Zaire strain of Ebola virus causing disease.

In the meantime, researchers continue to identify antibodies that confer broad immunity against Ebola virus. For that purpose, scientists sampled and characterized human antibodies from survivors of an Ebola outbreak. They identified two antibodies that cross-react against multiple species of the Ebola virus. This discovery might lead to the development of a broad-scale vaccine against the Ebola virus.