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

Graduate Program in Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Nature medicine 2010 Nov

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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.

Citation

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, Scheherazade Sadegh-Nasseri. A reductionist cell-free major histocompatibility complex class II antigen processing system identifies immunodominant epitopes. Nature medicine. 2010 Nov;16(11):1333-40