Previously the prediction of B-structure in myelin basic protein (MBP) led to the suggestion that MPB shares a threonine protein kinase recognition sequence with the C-terminus of the T-antigen, a regulatory, DNA-binding protein of the JC, BK, and SV40 viruses. This observation has raised important questions relating to (i) possible evolutionary relationships of MBP and the T-antigen sequences, (ii) the functional relationship of these sequences and the role of phosphorylation in these proteins, (iii) the possibility of immunological cross-reactions with potential for immunopathology in the CNS, and (iv) the pathological effects of latent JCV infection of the oligodendrocyte, the myelin-forming cell in the CNS. This past year a possible evolutionary relationship of the MBP site and the T-antigen C-terminus has been established. In addition, studies by K.-F. J. Chan (then of NICHD, ERR) established the Arg-Thr-Pro-Pro-Pro-Ser sequence of MBP as a protein kinase recognition site. Further, fluorescence studies in collaboration with S.J. Morris have provided strong experimental evidence for an organized structure in MBP which is consistent with the model originally predicted. Experiments utilizing antibodies raised in hamsters have established the existence of a cross-reactivity between the MBP and T-antigen triprolyl sequences. We have developed an ELISA inhibition assay to show that a synthetic decapeptide corresponding to the C-terminus of the JCV T-antigen strongly inhibits the binding of a hamster antiserum to MBP. A second antibody determinant in hamsters was identified in the peptide around Trp-117 which contains the encephalitogenic determinant for guinea pigs. Expression of T-antigen in human brain has so far been established for ordinary progressive multifocal leukoencephalopathy (PML) and for the severe form of PML identified in brains of some AIDS patients. The interaction between JCV and HTLV-III which leads to a high incidence and severe form of PML in AIDS remains to be identified. An initial search for T-antigen in multiple sclerosis (MS) brain using these methods was negative. However, more sensitive methods have now been developed, and are being applied to both frozen brain and kidney tissue from MS patients.
