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Recognition of Human Cytomegalovirus by Human Primary Immunoglobulins Identifies an Innate Foundation to an Adaptive Immune Response¹

The Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada

Most primates, including humans, are chronically infected with cospecifically evolved, potentially pathogenic CMV. Abs that bind a 10-aa linear epitope (antigenic determinant 2 site 1) within the extracellular domain of human CMV glycoprotein B neutralize viral infectivity. In this study, we show that genes generated by recombinations involving two well-conserved human germline V elements (IGHV3-30 and IGKV3-11), and IGHJ4, encode primary Ig molecules that bind glycoprotein B at this key epitope. These particular V_H, J_H, and V genes enable humans to generate through recombination and N nucleotide addition, a useful frequency of primary Igs that efficiently target this critical site on human CMV and thus confer an innate foundation for a specific adaptive response to this pathogen.