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comparison of antibody repertoires produced by hiv-1 infection, other chronic and acute infections, and systemic autoimmune disease产生的抗体体验比较hiv - 1感染,其他慢性和急性感染,系统性自身免疫性疾病.pdf

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Comparison of Antibody Repertoires Produced by HIV-1 Infection, Other Chronic and Acute Infections, and Systemic Autoimmune Disease 1 2¤a 3¤b 2¤c 3¤d Felix Breden *, Christa Lepik , Nancy S. Longo , Marinieve Montero , Peter E. Lipsky , Jamie K. Scott2,4* 1 Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, Canada, 2 Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada, 3 Repertoire Analysis Group, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, United States of America, 4 Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada Abstract Background: Antibodies (Abs) produced during HIV-1 infection rarely neutralize a broad range of viral isolates; only eight broadly-neutralizing (bNt) monoclonal (M)Abs have been isolated. Yet, to be effective, an HIV-1 vaccine may have to elicit the essential features of these MAbs. The V genes of all of these bNt MAbs are highly somatically mutated, and the VH genes of five of them encode a long ($20 aa) third complementarity-determining region (CDR-H3). This led us to question whether long CDR-H3s and high levels of somatic mutation (SM) are a preferred feature of anti-HIV bNt MAbs, or if other adaptive immune responses elicit them in general. Methodology and Principal Findings: We assembled a VH-gene sequence database from over 700 human MAbs of known antigen specificity isolated from chronic (viral) infections (ChI), acute (bacterial and viral) infections (AcI), and systemic autoimmune diseases (SAD), an
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