1304 Sequence Analysis of Borrelial Proteins

A strategy used by some pathogenic microorganisms for survival in their hosts is antigenic variation (1, 2). Borrelia hermsii, an etiologic agent o f relapsing fever, is a bacterium capable of manifesting 26 or more serotypes during the course of infection (3, 4). The spontaneous switching from one antigen type to another occurs at a rate estimated to be 10 -4 to 10 -~ per cell per generation (3). Al though antigenic variation by B. hermsii appears to be independent of the immune response, it is possible that host immunity or other factors play some role in determining which serotypes predominate in a given situation (3). Previous studies from our laboratory (5, 6) showed that antigenic variation is associated with change in a single, abundant , surface-exposed protein, referred to as a pI protein, which is hereafter designated as a variable major protein (VMP). 1 The VMPs of all serotypes of B. hermsii HS1 examined to date differed in their apparent molecular weights, their peptide maps, and their reactivities with serotype-specific polyclonal and monoclonal ant ibodies (4-6). In many respects, the phenomenology of antigenic variation in B. hermsii resembles that of the salivarian trypanosomes (7-9). Our efforts are toward understanding the molecular mechanisms used by B. hermsii, and probably other relapsing fever borreliae, to vary their surface antigens. The present analysis of VMP structure was designed to determine whether serotype-specific epitopes are confined to limited regions of the proteins and to fur ther assess the degree of structural relatedness between VMP. We now report on two borrelial VMP that were isolated, f ragmented, mapped with antibodies, and partially sequenced. The results indicate that VMP are the products of genes belonging to a polygene family.