A naturally processed HLA-DR-bound peptide from the IL-9 receptor alpha of HTLV-1-transformed T cells serves as a T helper epitope.
Human T cell leukemia virus type 1 (HTLV-1) induced adult T cell leukemia/lymphoma (ATLL) is usually a fatal lymphoproliferative malignant disease. Thus, the enhancement of T cell immunity to ATLL through the development of therapeutic vaccines using characterized T cell peptide epitopes could be of value. We isolated and characterized HLA-DR-bound peptides from HTLV-1-transformed T cells by fractionating on reverse-phase high performance liquid chromatography and Edman NH(2)-terminal sequencing and were able to identify five independent peptide sequences. One of the identified peptide sequences corresponded to a fragment of the human interleukin-9 receptor alpha (IL-9Rα), which is commonly expressed by HTLV-1-infected T cell lymphoma cells. Using a synthetic peptide corresponding to the identified IL-9Rα sequence, we generated antigen-specific CD4 helper T lymphocytes in vitro, which were restricted by HLA-DR15 or HLA-DR53 molecules and could recognize and kill HTLV-1+, IL-9Rα+ T cell lymphoma cells. These results indicate that IL-9Rα functions as T cell leukemia/lymphoma-associated antigen for CD4 T cells and that synthetic peptides such as the one described here could be used for T cell-based immunotherapy against IL-9Rα positive ATLL.
Department of Pathology, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1, Asahikawa, 078-8510, Japan. hiroya@asahikawa-med.ac.jp
Hiroya
H
Kobayashi
Takumi
T
Kumai
Satoshi
S
Hayashi
Yoshinari
Y
Matsuda
Naoko
N
Aoki
Keisuke
K
Sato
Shoji
S
Kimura
Esteban
E
Celis
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D006684:HLA-DR Antigens / Q000276:immunology* / Q000378:metabolism; D059810:HLA-DR Serological Subtypes / Q000276:immunology* / Q000378:metabolism; D059845:HLA-DRB4 Chains / Q000276:immunology* / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D053651:Receptors, Interleukin-9 / Q000276:immunology* / Q000378:metabolism; D020539:Sequence Analysis, Protein / Q000379:methods; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C106559:HLA-DR15 antigen; C050610:HLA-DR53; D059845:HLA-DRB4 Chains; C508045:IL9R protein, human; D053651:Receptors, Interleukin-9