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 language | English (US) |
|---|---|
| Pages (from-to) | 1333-1340 |
| Number of pages | 8 |
| Journal | Nature Medicine |
| Volume | 16 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 2010 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - A reductionist cell-free major histocompatibility complex class II antigen processing system identifies immunodominant epitopes
AU - Hartman, Isamu Z.
AU - Kim, Aeryon
AU - Cotter, Robert J.
AU - Walter, Kimberly
AU - Dalai, Sarat K.
AU - Boronina, Tatiana
AU - Griffith, Wendell
AU - Lanar, David E.
AU - Schwenk, Robert
AU - Krzych, Urszula
AU - Cole, Robert N
AU - Sadegh-Nasseri, Scheheraza
PY - 2010/11
Y1 - 2010/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=78149357976&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78149357976&partnerID=8YFLogxK
U2 - 10.1038/nm.2248
DO - 10.1038/nm.2248
M3 - Article
C2 - 21037588
AN - SCOPUS:78149357976
VL - 16
SP - 1333
EP - 1340
JO - Nature Medicine
JF - Nature Medicine
SN - 1078-8956
IS - 11
ER -