A type-specific B cell epitope at the apex of Outer surface protein C (OspC) of the Lyme disease spirochete, Borreliella burgdorferi

Abstract

Broadly protective immunity to the Lyme disease spirochete, Borreliella burgdorferi, is constrained by an overwhelming antibody response against type-specific epitopes on Outer surface protein C (OspC), a homodimeric helix-rich lipoprotein essential for early stages of spirochete dissemination in vertebrate hosts. However, the molecular basis for type-specific immunity has not been fully elucidated. In this report, we produced and characterized an OspC mouse monoclonal antibody, 8C1, that recognizes native and recombinant OspC type A (OspCA) but not OspC types B or K, and arrests B. burgdorferi motility independent of complement. Epitope mapping by HDX-MS localized 8C1s epitope to a protruding ridge on the apex of OspCA -helix 3 (residues 130-150) previously known to be an immunodominant region of the molecule. Alanine scanning pinpointed 8C1s core binding motif to a solvent exposed patch consisting of residues K141 H142 T143 D144. In parallel, analysis of 26 Lyme disease positive serum samples confirmed antibody reactivity with this region of OspCA, with residues E140 and D144 as being most consequential. Our results underscore the importance of -helix 3 as a target of type-specific epitopes on OspCA across mice and humans that should be taken into consideration in Lyme disease vaccine design.