'Determinant spreading' (or epitope spreading) describes an amplification phenomenon observed in inflammatory autoimmune disease in which the original T cell response diversifies through induction of T cells against additional autoantigenic determinants. The response to the initiating determinant is followed by 'intramolecular' spreading, activation of T cells specific for other, often previously cryptic or subdominant self determinants (defined below) within the same antigen during the course of chronic and progressive disease; 'intermolecular' spreading involves determinants on other unrelated self antigens.

A multideterminant protein antigen possesses dominant, subdominant and cryptic T cell determinants. The dominant determinants are those that are most efficiently processed and presented from native antigen, whereas cryptic determinants arc inefficiently processed and/or presented, or not at all.

Therefore, a response to a cryptic determinant can only be induced by immunization with the appropriate peptide which usually does not need additional processing. The subdominant determinants lie on the continuum between these two categories.

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