Antibodies are proteins produced by the immune system to neutralize foreign invaders like bacteria and viruses. They target specific molecules on an invader’s surface, known as antigens. This interaction is often compared to a lock and key, where a specific antibody fits only one antigen. However, an antibody can sometimes bind to an antigen different from its original target. This is called cross-reactivity, and it occurs when two different antigens share structurally similar features.
The Mechanism of Antibody Recognition
An antibody binds to a small region on an antigen’s surface called an epitope. The binding is dictated by the three-dimensional shape and chemical properties of both the antibody and the epitope. For binding to occur, the antibody’s binding site must be a near-perfect structural and chemical match.
Cross-reactivity happens when different antigens possess epitopes that are highly similar in structure, a concept known as molecular mimicry. For example, a molecule from a pathogen might share structural similarities with a molecule in the host’s body. An antibody produced against the pathogen may then mistakenly bind to the body’s own cells due to this resemblance.
The degree of similarity required can vary, but this structural homology is the basis for cross-reactivity. This enables a single antibody to interact with multiple, distinct antigens. This process can have both beneficial and detrimental consequences for the host.
Protective Cross-Reactivity in Immunity
Cross-reactivity can provide a broad range of protection against related pathogens. This occurs when immunity developed against one pathogen confers protection against a different, but similar, one.
A famous historical example is the basis of the first vaccine. Edward Jenner observed that milkmaids who contracted the mild cowpox disease were immune to the deadly smallpox virus. Because the two viruses share similar antigenic structures, antibodies developed against cowpox could also neutralize the smallpox virus.
A more modern example involves coronaviruses. Research suggests antibodies from a past infection with a common cold-causing coronavirus may offer protection against a related one like SARS-CoV-2. This pre-existing immunity from cross-reactivity can lead to a milder disease course or prevent infection.
Detrimental Cross-Reactivity in Disease
While protective, cross-reactivity can also lead to harmful immune responses, contributing to allergies and autoimmune diseases. In these cases, the immune system attacks harmless substances or the body’s own tissues. This misdirected response is a factor in several chronic conditions.
Allergies
A clear example is Oral Allergy Syndrome (OAS), which affects individuals with pollen allergies. The proteins in certain raw fruits, vegetables, and nuts are structurally similar to proteins in pollen. When a person with a birch pollen allergy eats a raw apple, their immune system mistakes the apple protein for the pollen protein. This triggers an allergic reaction with itching and swelling of the mouth, lips, and throat because the antibodies cross-react with the similar proteins in the food.
Autoimmune Diseases
Cross-reactivity is also a mechanism in the development of autoimmune diseases. A classic example is rheumatic fever, which can develop after a Streptococcus pyogenes infection (strep throat). The immune system produces antibodies to fight the bacteria. However, certain bacterial proteins share structural similarities with proteins in human tissues like the heart valves, joints, and brain. These antibodies, intended for the bacteria, can cross-react and attack human tissues, leading to inflammation and damage. This autoimmune attack causes the symptoms of rheumatic fever, such as carditis and arthritis.
Impact on Medical Testing
Cross-reactive antibodies can impact medical diagnostics, sometimes causing false-positive results. This occurs when a test detects antibodies that are cross-reacting with the target antigen, even though they were generated against a different condition.
This has been an issue in diagnosing infectious diseases. For example, early tests for Lyme disease and syphilis had cross-reactivity problems, where antibodies for one could trigger a positive result for the other. Other conditions like mononucleosis can also produce antibodies that cross-react in tests for Lyme disease, leading to inaccurate results.
To address this, modern diagnostic assays are engineered for higher specificity. They use purified antigens or specific antigen fragments that are less likely to cause cross-reactions. Confirmatory tests, like the Western blot, are often used to verify initial positive results and distinguish them from those caused by cross-reactivity.