MURINE V-LAMBDA-X AND V-LAMBDA-X-CONTAINING ANTIBODIES BIND HUMAN MYELIN BASIC-PROTEIN

Myelin basic protein (MBP) is highly immunogenic and a known autoantig en capable of inducing experimental allergic encephalomyelitis (EAE), the animal model of multiple sclerosis. We have previously described a murine monoclonal antibody (mAb), F28C4, directed against the encepha litogenic MBP peptide acetyl (Ac) 1-9, which contains a V lambda x lig ht chain. Considering the rarity of V lambda x usage, we determined wh ether other Abs having V lambda x light chains shared similar antigen (Ag) specificity. We screened a panel of V lambda x-containing monoclo nal and polyclonal Abs, of unknown specificity for reactivity with MBP . All such Ab, but not heavy chain isotype matched controls, bound MBP but were not polyreactive with other potential self Ags. The binding of a recombinant form of V lambda x alone to MBP demonstrated the impo rtant contribution of the V lambda x light chain to the reaction. With the exception of mAb F28C4 which recognizes MBP Ac1-9, the epitope sp ecificity of all other V lambda x-bearing Abs was localized to MBP res idues 25-34. These results demonstrate a unique association between V lambda x expression and MBP reactivity. Given that V lambda x shares s equence homology with T cell receptors (TCR) from encephalitogenic T l ymphocytes, these results imply a potential role for V lambda x in the pathogenesis of EAE.