We have assessed the complexity in T cell recognition of the immunodominant 35-55 region of myelin oligodendrocyte glycoprotein (MOG) in C57BL/6 mice. Immunization with the p35-55 peptide generated two types of T cell, recognizing either a cryptic, or a naturally-processed epitope. Clear differences in the recognition of residues within a core sequence of 40-48 were observed. The majority of the p35-55-reactive repertoire in vivo appeared responsive to the intact autoantigen, supporting the notion of a failure of central tolerance to this region of MOG. Our data also provide a basis for exploring the requirements for antigen processing of MOG.