Fridkis-Hareli, Masha and Reche, Pedro A and Reinherz, Ellis L (2004) Peptide variants of viral CTL epitopes mediate positive selection and emigration of Ag-specific thymocytes in vivo. Journal of Immunology (Baltimore, Md. : 1950), 173 (2). pp. 1140-50. ISSN 0022-1767
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.
|Subjects:||Medical sciences > Medicine > Immunology|
Medical sciences > Biology > Molecular biology
|Deposited On:||06 Aug 2009 10:11|
|Last Modified:||06 Feb 2014 08:23|
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