A V-LAMBDA-X-BEARING MONOCLONAL-ANTIBODY WITH SIMILAR SPECIFICITY ANDSEQUENCE TO ENCEPHALITOGENIC T-CELL RECEPTORS

The fine specificity of mAb F28C4 to myelin basic protein (MBP), acety l residues 1-9, has been compared with the previously described specif icity of an encephalitogenic T cell clone, PJR-25. F28C4 has been foun d to express a cross-reactive idiotope (CRI) that is shared with MBP a cetyl peptide 1-9-specific TCR. The CRI seems to be located at or near the Ag-combining site of F28C4 and the TCR and, thus, might possibly result from overlapping epitope specificity. We tested the fine epitop e specificity of F28C4 by using alanine-substituted peptide analogues and found that residues critical for TCR recognition, Gln(3) and Pro(6 ), are also necessary for F28C4 recognition. By using nuclear magnetic resonance, we found that the MBP acetyl peptide 1-9 binds F28C4 in an extended conformation and that the central residues are more tightly bound than the terminal residues, much like the MBP-TCR interaction. F urthermore, sequence homology (75% overall) was found between the regi ons that contained CDR3 of F28C4 V-L and V-H and the VDJ junction of t he TCR V beta. This homology is not shared by other Ig CDR3 regions an d arises, in part, because F28C4 uses an unusual V lambda light chain, V lambda x. Thus, F28C4 shares a CRI with the TCRs, possibly as a res ult of having similar fine epitope specificity and sequence homology. The anti-CRI mAb can down-modulate experimental allergic encephalomyel itis; thus, it is possible that Abs that are similar to F28C4 may play an important immunoregulatory role in experimental allergic encephalo myelitis in vivo.