Recognition of human cytomegalovirus by human primary immunoglobulins identifies an innate foundation to an adaptive immune response.
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(kappa) 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.
McLean
Gary R
GR
The Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
Olsen
Ole A
OA
Watt
Ian N
IN
Rathanaswami
P
P
Leslie
Kevin B
KB
Babcook
John S
JS
Schrader
John W
JW
D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000956:Antigens, Viral / Q000235:genetics; D001483:Base Sequence; D003062:Codon / Q000235:genetics; D003587:Cytomegalovirus / Q000276:immunology*; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007136:Immunoglobulins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology
D000914:Antibodies, Viral; D000956:Antigens, Viral; D003062:Codon; D018076:DNA, Complementary; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D007136:Immunoglobulins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus