Autoreactivity profiles of influenza hemagglutinin broadly neutralizing antibodies

被引：47

作者：

Bajic, Goran ^{[1
]}

van der Poel, Cees E. ^{[2
]}

Kuraoka, Masayuki ^{[3
]}

Schmidt, Aaron G. ^{[4
,5
]}

Carroll, Michael C. ^{[2
]}

Kelsoe, Garnett ^{[3
,6
]}

Harrison, Stephen C. ^{[1
,7
]}

机构：

[1] Harvard Med Sch, Boston Childrens Hosp, Lab Mol Med, Boston, MA 02115 USA

[2] Harvard Med Sch, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA

[3] Duke Univ, Dept Immunol, Durham, NC 27710 USA

[4] Harvard Med Sch, Dept Microbiol, Boston, MA 02115 USA

[5] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA

[6] Duke Univ, Duke Human Vaccine Inst, Durham, NC 27710 USA

[7] Howard Hughes Med Inst, Boston, MA 02115 USA

来源：

SCIENTIFIC REPORTS | 2019年 / 9卷 / 1期

关键词：

RECEPTOR-BINDING; ANTIPHOSPHOLIPID SYNDROME; A VIRUSES; B-CELLS; HIV-1; RESPONSES; VACCINE; COMPLEX; FUSION; SITE;

D O I：

10.1038/s41598-019-40175-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Epitope-focused approaches for selective clonal induction of broadly neutralizing antibodies (bnAbs) inform most current vaccine strategies for influenza virus and other rapidly evolving pathogens. The two conserved epitopes on the influenza hemagglutinin (HA) - the "stem" and the receptor-binding site (RBS) on the "head" - are the focus of the current "universal" influenza vaccine development efforts. Because stem-directed serum bnAbs are much less abundant than head-directed ones, we hypothesized that the HA stem bnAbs may be autoreactive and thus eliminated through the mechanisms of selftolerance. We compared autoreactivity profiles of a set of stem and head-directed bnAbs. Most of the stem bnAbs we examined bound autoantigens; several showed staining of HEp-2 cells. A smaller proportion of the head-directed bnAbs were polyreactive. Gene usage did not correlate with autoreactivity. We suggest that complex foreign antigens may often have surface patches resembling some host epitope; our results indicate that HA stem epitopes resemble a host epitope more frequently than does the RBS.

引用

页数：9

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