Epitope spreading is the process by which an autoimmune response expands from an initial target to additional self-antigens. It begins when tissue damage releases proteins that were previously hidden from the immune system. Those proteins are taken up by antigen-presenting cells, processed, and displayed as new peptides. Lymphocytes specific for these newly exposed epitopes are then activated and join the attack.
The consequence is amplification. What started as a response to one self-peptide becomes a response to several, and each new specificity adds more tissue damage, which releases more antigens, which recruits more specificities. The process can become self-sustaining. Epitope spreading explains why autoimmune diseases often worsen over time and why the original trigger may no longer be required once the response has broadened. It also means that the set of targets at diagnosis may differ from the set of targets later in the disease.