THE NATURE OF CRYPTIC EPITOPES WITHIN THE SELF-ANTIGEN MYELIN BASIC-PROTEIN

Mechanisms that allow potentially autoreactive T cells to escape centr al tolerance and persist in the peripheral lymphoid organs of healthy individuals are poorly defined. It has been proposed that such cells a re specific for epitopes which normally are not well presented to the immune system or, in other words, are cryptic. We have used synthetic peptides to define potential T cell epitopes within the N-terminal por tion of myelin basic protein (MBP). These were defined in terms of the ir relative affinity for the MHC-restriction element 1-A(U) and their ability to activate T cells in mice of the H-2(U) haplotype. Three epi topes were identified, one of which corresponded to the known dominant N-terminal epitope (Ac1-9). The other two epitopes (9-20 and 5-20) bo und to their MHC-restriction element with relatively high affinity but were cryptic, as defined by the poor response to these epitopes follo wing immunization with intact MBP. Even the longer of these two epitop es did not induce autoimmune encephalomyelitis in H-2(U) mice. These r esults demonstrate that antigen processing can control both the induct ion of and effector function of autoreactive T cells, and is therefore a principal mechanism involved in limiting the autoreactive T cell re pertoire.