A reductionist cell-free major histocompatibility complex class II antigen processing system identifies immunodominant epitopes

被引：44

作者：

Hartman, Isamu Z. ^{[1
]}

Kim, AeRyon ^{[1
]}

Cotter, Robert J. ^{[2
]}

Walter, Kimberly ^{[3
]}

Dalai, Sarat K. ^{[3
]}

Boronina, Tatiana ^{[4
]}

Griffith, Wendell ^{[2
]}

Lanar, David E. ^{[5
]}

Schwenk, Robert ^{[5
]}

Krzych, Urszula ^{[5
]}

Cole, Robert N. ^{[4
,6
]}

Sadegh-Nasseri, Scheherazade ^{[1
,3
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Grad Program Immunol, Baltimore, MD 21218 USA

[2] Johns Hopkins Univ, Sch Med, Dept Pharmacol, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA

[5] Walter Reed Army Inst Res, Div Malaria Vaccine Dev, Silver Spring, MD USA

[6] Johns Hopkins Univ, Sch Med, Mass Spectrometry & Prote Facil, Inst Basic Biomed Sci, Baltimore, MD USA

来源：

NATURE MEDICINE | 2010年 / 16卷 / 11期

基金：

美国国家科学基金会;

关键词：

LIVER-STAGE ANTIGEN-1; COLLAGEN TYPE-II; HLA-DM; PLASMODIUM-FALCIPARUM; MASS-SPECTROMETRY; T-CELLS; REMNANT EPITOPES; MHC MOLECULES; GELATINASE-B; CATHEPSIN-S;

D O I：

10.1038/nm.2248

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Immunodominance is defined as restricted responsiveness of T cells to a few selected epitopes from complex antigens. Strategies currently used for elucidating CD4(+) T cell epitopes are inadequate. To understand the mechanism of epitope selection for helper T cells, we established a cell-free antigen processing system composed of defined proteins: human leukocyte antigen-DR1 (HLA-DR1), HLA-DM and cathepsins. Our reductionist system successfully identified the physiologically selected immunodominant epitopes of two model antigens: hemagglutinin-1 (HA1) from influenza virus (A/Texas/1/77) and type II collagen (CII). When applied for identification of new epitopes from a recombinant liver-stage antigen of malaria falciparum (LSA-NRC) or HA1 from H5N1 influenza virus ('avian flu'), the system selected single epitopes from each protein that were confirmed to be immunodominant by their capacity to activate CD4(+) T cells from H5N1-immunized HLA-DR1-transgenic mice and LSA-NRC-vaccinated HLA-DR1-positive human volunteers. Thus, we provide a new tool for the identification of physiologically relevant helper T cell epitopes from antigens.

引用

页码：1333 / U192

页数：9

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