T-CELL RESPONSES TO MYELIN BASIC-PROTEIN IN NORMAL AND MBP-DEFICIENT MICE

BALB/c mice are resistant to the development of experimental autoimmun e encephalomyelitis (EAE) after immunization with myelin basic protein (MBP). Previous studies of BALB/c mice suggest that MBP-specific T-ce lls can eventually be cloned from these mice, although they are either initially present in very low frequencies or are functionally anergic . To determine what role endogenous MBP expression plays in shaping th e BALB/c T-cell repertoire, MBP-deficient BALB/c mice were constructed by breeding the shiverer (shi/shi) mutation onto the BALB/c backgroun d. These mice lack all conventional isoforms of MBP due to a deletion of MBP exons 3-7. Studies of the MBP-directed response of these mice s uggest that endogenous MBP expression is directly responsible for EAE resistance in BALB/c mice, by quantitatively affecting expression of t he T-cell repertoire. In contrast to wild-type BALB/c T-cells. unclone d T-cells from BALB/c shi/shi mice immunized with MBP proliferate in v itro to MBP and MBP peptides 59-76 and 89-101 and are able to induce s evere EAE upon transfer to BALB/c recipients expressing MBP. (C) 1998 Elsevier Science B.V.