Characterizing the Functional Autoreactivity and Polyspecificity of the MPER-Specific bNAb 4E10 and an Ensemble of Its Germline-Encoded Precursors

Background: The bNAb 4E10 recognizes an epitope in the HIV gp41 MPER. Previous attempts at eliciting 4E10, by vaccination with envelope-derived or reverse-engineered immunogens, have failed, but have yielded tight-binding, computationally-designed 4E10 'epitope-scaffolds' that can elicit epitope-specific responses. The ontogeny of functional 4E10-equivalent responses has been presumed to be blocked by inherent autoreactivity. Previously identified candidate 4E10 autoantigens include the mitochondrial lipid cardiolipin and a nuclear splicing factor, 3B3.