Probing for cerebrospinal fluid antibody specificities by a panel of random peptide libraries

In a state of health the central nervous system is nearly devoid of macrophages, T and B cells. However, such cells are required to initiate the inflammation associated with multiple sclerosis (MS). An important issue in understanding the pathogenesis of such conditions is to fully define the T and B cell specificities. Using random peptide libraries, we have analysed the cerebrospinal fluid antibody specificities within one oligoclonal "band" from a patient with MS. The selected peptides from a 6-mer library revealed two peptide motifs S (S/T/Q) (R/S) (N/G) FP and PRn (G/P) FF. Interestingly, the first motif was also selected from a 15-mer library, while the second motif was selected from the 9-mer library. In addition, distinct but structurally related peptides to the mentioned motifs were also selected. Surprisingly, a SwissProt search with these motifs revealed a significant linear homology with collagen proteins, the 68 kDa neurofilament protein, versican and other proteins from viruses such as herpes simplex virus, human cytomegalovirus and human papillomavirus. Thus, the observation that antibodies present within one oligoclonal immunoglobulin band would recognize peptides, some that might be related by only the structure, raises the question of the involvement of multiple pathogens in MS.