Abstract
Potent graft-versus-leukemia (GVL) effects can be mediated by donor-derived T cells recognizing minor histocompatibility antigens (mHags) in patients treated with donor lymphocyte infusion (DLI) for relapsed hematologic malignancies after HLA-matched allogeneic stem cell transplantation (alloSCT). Donor-derived T cells, however, may not only induce GVL, but also mediate detrimental graft-versus-host disease (GVHD). Because HLA-class II is under noninflammatory conditions predominantly expressed on hematopoietic cells, CD4+ T cells administered late after alloSCT may selectively confer GVL without GVHD. Although a broad range of different HLA-class I-restricted mHags have been identified, the first 2 autosomal HLA-class II-restricted mHags have only recently been characterized. By screening a recombinant bacteria cDNA expression library, we identified 4 new HLA-class II-restricted mHags recognized by CD4+ T cells induced in a patient with relapsed chronic myeloid leukemia who achieved long-term complete remission and experienced only mild GVHD of the skin after DLI. All CD4+ T cells were capable of recognizing the mHags presented by HLA-DR surface molecules on primary hematopoietic cells, but not on skin-derived (cytokine-treated) fibroblasts. The selective recognition of hematopoietic cells as well as the balanced population frequencies and common HLA-DR restriction elements make the novel mHags possible targets for development of immunotherapeutic strategies.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD / genetics
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Antigens, CD / immunology
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CD4-Positive T-Lymphocytes / immunology*
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DNA, Complementary
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Enzyme-Linked Immunosorbent Assay
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Epitopes
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Fibroblasts / immunology
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Fibroblasts / metabolism
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Focal Adhesion Kinase 2 / genetics
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Focal Adhesion Kinase 2 / immunology
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Graft vs Host Disease / immunology*
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Graft vs Leukemia Effect / immunology*
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HLA-DR Antigens / immunology*
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Hematopoietic Stem Cell Transplantation
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Hematopoietic System / cytology
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Hematopoietic System / immunology*
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Histocompatibility Antigens Class I / genetics
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Histocompatibility Antigens Class I / immunology
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Humans
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Lectins, C-Type / genetics
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Lectins, C-Type / immunology
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology*
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy
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Methylenetetrahydrofolate Dehydrogenase (NADP) / genetics
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Methylenetetrahydrofolate Dehydrogenase (NADP) / immunology
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Minor Histocompatibility Antigens / immunology*
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Polymorphism, Single Nucleotide
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / immunology
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Skin / cytology
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Skin / immunology
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Skin / metabolism
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Transplantation, Homologous
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Tumor Cells, Cultured
Substances
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Antigens, CD
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DEC-205 receptor
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DNA, Complementary
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Epitopes
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HLA-DR Antigens
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Histocompatibility Antigens Class I
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Lectins, C-Type
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MR1 protein, human
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Minor Histocompatibility Antigens
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Receptors, Cell Surface
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MTHFD1 protein, human
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Methylenetetrahydrofolate Dehydrogenase (NADP)
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Focal Adhesion Kinase 2
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PTK2B protein, human