| First Author | Hartman IZ | Year | 2010 |
| Journal | Nat Med | Volume | 16 |
| Issue | 11 | Pages | 1333-40 |
| PubMed ID | 21037588 | Mgi Jnum | J:166137 |
| Mgi Id | MGI:4839827 | Doi | 10.1038/nm.2248 |
| Citation | Hartman IZ, et al. (2010) A reductionist cell-free major histocompatibility complex class II antigen processing system identifies immunodominant epitopes. Nat Med 16(11):1333-40 |
| abstractText | 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. |
