Journal
CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 61, Issue 12, Pages 2215-2225Publisher
SPRINGER
DOI: 10.1007/s00262-012-1284-7
Keywords
HTLV-1; IL-9 receptor; Adult T cell leukemia/lymphoma; Tumor antigens; Major histocompatibility complex class II; CD4 helper T lymphocytes
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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 NH2-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-9R alpha), which is commonly expressed by HTLV-1-infected T cell lymphoma cells. Using a synthetic peptide corresponding to the identified IL-9R alpha 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-9R alpha+ T cell lymphoma cells. These results indicate that IL-9R alpha 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-9R alpha positive ATLL.
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