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

Isamu Z. Hartman, Aeryon Kim, Robert J. Cotter, Kimberly Walter, Sarat K. Dalai, Tatiana Boronina, Wendell Griffith, David E. Lanar, Robert Schwenk, Urszula Krzych, Robert N Cole, Scheheraza Sadegh-Nasseri

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1333-1340
Number of pages8
JournalNature Medicine
Volume16
Issue number11
DOIs
StatePublished - Nov 2010

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Immunodominant Epitopes
Histocompatibility Antigens Class II
Antigen Presentation
Major Histocompatibility Complex
Epitopes
HLA Antigens
T-cells
Antigens
T-Lymphocyte Epitopes
Processing
Helper-Inducer T-Lymphocytes
Viruses
HLA-DR1 Antigen
H5N1 Subtype Influenza A Virus
T-Lymphocytes
Cathepsins
Influenza in Birds
Collagen Type II
Falciparum Malaria
Influenza A virus

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

A reductionist cell-free major histocompatibility complex class II antigen processing system identifies immunodominant epitopes. / Hartman, Isamu Z.; Kim, Aeryon; Cotter, Robert J.; Walter, Kimberly; Dalai, Sarat K.; Boronina, Tatiana; Griffith, Wendell; Lanar, David E.; Schwenk, Robert; Krzych, Urszula; Cole, Robert N; Sadegh-Nasseri, Scheheraza.

In: Nature Medicine, Vol. 16, No. 11, 11.2010, p. 1333-1340.

Research output: Contribution to journalArticle

Hartman, IZ, Kim, A, Cotter, RJ, Walter, K, Dalai, SK, Boronina, T, Griffith, W, Lanar, DE, Schwenk, R, Krzych, U, Cole, RN & Sadegh-Nasseri, S 2010, 'A reductionist cell-free major histocompatibility complex class II antigen processing system identifies immunodominant epitopes', Nature Medicine, vol. 16, no. 11, pp. 1333-1340. https://doi.org/10.1038/nm.2248
Hartman, Isamu Z. ; Kim, Aeryon ; Cotter, Robert J. ; Walter, Kimberly ; Dalai, Sarat K. ; Boronina, Tatiana ; Griffith, Wendell ; Lanar, David E. ; Schwenk, Robert ; Krzych, Urszula ; Cole, Robert N ; Sadegh-Nasseri, Scheheraza. / A reductionist cell-free major histocompatibility complex class II antigen processing system identifies immunodominant epitopes. In: Nature Medicine. 2010 ; Vol. 16, No. 11. pp. 1333-1340.
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