A NEUTRALIZING EPITOPE OF HUMAN PAPILLOMAVIRUS TYPE-11 IS PRINCIPALLYDESCRIBED BY A CONTINUOUS SET OF RESIDUES WHICH OVERLAP A DISTINCT LINEAR, SURFACE-EXPOSED EPITOPE

A panel of monoclonal antibodies (MAbs) which neutralize human papillo mavirus type 11 (HPV11) in the athymic mouse xenograph neutralization assay and bind HPV11 virus like particles (VLPs) has been described. W e recently presented evidence that the Gly(131)-Tyr(132) residues of t he major capsid protein L1 confer type Ii-specific binding. However, r esidues distally located on the primary L1 sequence also were shown to affect binding. This poses the question whether the epitope is princi pally centered in the region of Gly(131)-Tyr(132) or, alternatively, i s comprised of diversely located residues which come into proximity on ly upon proper assembly, We analyzed the result of numerous substituti ons located between Tyr(123) and Val(142) of the HPV11 L1 sequence, We show that substitutions at five positions result in loss of binding f or one or more of these MAbs by an enzyme-linked immunosorbent assay w hich measures antibody binding to VLPs. We demonstrate that binding of these MAbs is redirected to HPV16 VLPs which harbor eight type Ii-lik e substitutions within the homologous region, Three of these substitut ions did not affect binding when individually substituted in HPV11 but yet were still required to transfer binding to substituted HPV16 VLPs , The results demonstrate that the epitope for this class of neutraliz ing MAbs, although conformational and requiring VLP assembly for prese ntation, principally lies along a 20-residue stretch of the L1 major c apsid protein. This targets the region for evaluation of the possibili ty of receptor binding and suggests possibilities for the design of pe ptide inhibitors of virus infectivity.