EpitopeSpreading

Epitope spreading refers to a diversification of the adaptive immune response from an initial dominant epitope toward additional epitopes. It can occur within the same antigen (intramolecular spreading) or across different antigens (intermolecular spreading). The concept is frequently discussed in the contexts of chronic infections and autoimmune diseases, where the immune response broadens over time beyond the first targeted epitopes.

Mechanistically, epitope spreading is thought to arise when tissue damage or persistent antigen exposure leads to the release of cryptic or subdominant epitopes. Antigen-presenting cells process these epitopes and present them to T cells, expanding helper T cell responses and, in turn, helping B cells produce antibodies against new epitopes. This creates a feed-forward loop in which ongoing immune activation exposes additional targets, potentially widening autoreactivity or antiviral recognition.

Epitope spreading has been described in several diseases. In autoimmune conditions such as multiple sclerosis, its progression has been linked to the diversification of autoreactive responses and disease evolution. Similar patterns have been observed in systemic lupus erythematosus and rheumatoid arthritis. In chronic infections, spreading may reflect persistent antigenic stimulation and influence the trajectory of the immune response.

The concept has practical implications for treatment and vaccine design. Therapeutic strategies that focus on a single antigen or epitope may be undermined by spreading, while approaches that account for epitope diversity may achieve broader or more durable control of disease.