October 7, 2011

Diversity key in antibody repertoire

Antibodies to the 2009 H1N1 influenza strain reveal new insights into how antibody diversity forms and functions, with possible implications for designing flu vaccines.

antibodies
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Having antibodies diverse enough to neutralize a range of viruses is advantageous for preventing reinfection. But the molecular features that underlie this diversity (and how it is generated) are poorly understood.

James Crowe Jr., Ingram Professor of Cancer Research and professor of pathology, microbiology and immunology, and colleagues previously isolated an antibody to 1918 influenza (called 2D1) that could also neutralize the 2009 H1N1 strain. In the Oct. 1 Journal of Immunology, they report the isolation and characterization of a panel of five antibodies from a survivor of the 2009 H1N1 pandemic. Although the 2009 antibodies bound the same region of the virus (the Sa site) as 2D1, they inhibited a broader panel of H1N1 strains than did 2D1. The 2009 antibodies also shared a gene segment in the antibodies’ “heavy chains” – which differed from the gene segment identified in 2D1. High throughput gene sequencing suggested that the antibodies arose independently, but converged toward similar amino acid sequences.

The findings provide new insights into how antibody diversity forms and functions – and could potentially lead to better methods of designing flu vaccines rationally.

The research was supported by grants from the National Institute of Allergy and Infectious Diseases, the National Center for Research Resources, the National Cancer Institute, the National Institute of Diabetes and Digestive and Kidney Disorders, and the National Eye Institute.