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Identification of 4 new HLA-DR-restricted minor histocompatibility antigens as hematopoietic targets in antitumor immunity.
Stumpf, Anita N; van der Meijden, Edith D; van Bergen, Cornelis A M; Willemze, Roel; Falkenburg, J H Frederik; Griffioen, Marieke.
Afiliação
  • Stumpf AN; Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
Blood ; 114(17): 3684-92, 2009 Oct 22.
Article em En | MEDLINE | ID: mdl-19706888
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Leucemia Mielogênica Crônica BCR-ABL Positiva / Linfócitos T CD4-Positivos / Antígenos HLA-DR / Antígenos de Histocompatibilidade Menor / Efeito Enxerto vs Leucemia / Doença Enxerto-Hospedeiro / Sistema Hematopoético Tipo de estudo: Diagnostic_studies Limite: Humans Idioma: En Revista: Blood Ano de publicação: 2009 Tipo de documento: Article País de afiliação: Holanda

Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Leucemia Mielogênica Crônica BCR-ABL Positiva / Linfócitos T CD4-Positivos / Antígenos HLA-DR / Antígenos de Histocompatibilidade Menor / Efeito Enxerto vs Leucemia / Doença Enxerto-Hospedeiro / Sistema Hematopoético Tipo de estudo: Diagnostic_studies Limite: Humans Idioma: En Revista: Blood Ano de publicação: 2009 Tipo de documento: Article País de afiliação: Holanda