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Título:
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Peptide variants of viral CTL epitopes mediate positive selection and emigration of Ag-specific thymocytes in vivo
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Autores:
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Fridkis-Hareli, Masha ;
Reche, Pedro A ;
Reinherz, Ellis L
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Tipo de documento:
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texto impreso
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Fecha de publicación:
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2004
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Dimensiones:
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application/pdf
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Nota general:
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info:eu-repo/semantics/openAccess
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Idiomas:
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Palabras clave:
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Estado = Publicado
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Materia = Ciencias Biomédicas: Medicina: Inmunología
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Materia = Ciencias Biomédicas: Biología: Biología molecular
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Tipo = Artículo
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Resumen:
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During development, thymocytes carrying TCRs mediating low-affinity interactions with MHC-bound self-peptides are positively selected for export into the mature peripheral T lymphocyte pool. Thus, exogenous administration of certain altered peptide ligands (APL) with reduced TCR affinity relative to cognate Ags may provide a tool to elicit maturation of desired TCR specificities. To test this "thymic vaccination" concept, we designed APL of the viral CTL epitopes gp33-41 and vesicular stomatitis virus nucleoprotein octapeptide N52-59 relevant for the lymphocytic choriomeningitis virus-specific P14- and vesicular stomatitis virus-specific N15-TCRs, respectively, and examined their effects on thymocytes in vivo using irradiation chimeras. Injection of APL into irradiated congenic (Ly-5.1) mice, reconstituted with T cell progenitors from the bone marrow of P14 RAG2(-/-) (Ly-5.2) or N15 RAG2(-/-) (Ly-5.2) transgenic mice, resulted in positive selection of T cells expressing the relevant specificity. Moreover, the variants led to export of virus-specific T cells to lymph nodes, but without inducing T cell proliferation. These findings show that the mature T cell repertoire can be altered by in vivo peptide administration through manipulation of thymic selection.
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En línea:
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https://eprints.ucm.es/id/eprint/9335/1/22.Fridkis_Reche_etal_JI_2004.pdf
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