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Efficient T cell repertoire selection in tetraparental chimeric mice independent of thymic epithelial MHC.


ABSTRACT: Nonthymic epithelial cells were compared with thymic epithelial cells for their role in T cell repertoire selection. Tetraparental aggregation chimeras were generated from T and B cell-deficient mice (H-2(d) SCID or H-2(b) Rag-/-) and thymus-deficient nude mice (H-2(b) or H-2(d)). These tetraparental mice showed primary protective CD8(+) T cell responses, after lymphocytic choriomeningitis virus infection, that were peptide-specifically restricted to either thymic or nonthymic epithelial MHC at comparable levels. These chimeras also mounted neutralizing IgG responses dependent on cognate CD4(+) T helper cell activity restricted to nonthymic epithelial MHC. Therefore, in contrast to earlier results with irradiation or thymus chimeras, these relatively undisturbed tetraparental mice reveal that the MHC of nonthymic epithelial cells efficiently selects a functional T cell repertoire.

SUBMITTER: Martinic MM 

PROVIDER: S-EPMC149924 | biostudies-literature | 2003 Feb

REPOSITORIES: biostudies-literature

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Efficient T cell repertoire selection in tetraparental chimeric mice independent of thymic epithelial MHC.

Martinic Marianne M MM   Rülicke Thomas T   Althage Alana A   Odermatt Bernhard B   Höchli Matthias M   Lamarre Alain A   Dumrese Tilman T   Speiser Daniel E DE   Kyburz Diego D   Hengartner Hans H   Zinkernagel Rolf M RM  

Proceedings of the National Academy of Sciences of the United States of America 20030206 4


Nonthymic epithelial cells were compared with thymic epithelial cells for their role in T cell repertoire selection. Tetraparental aggregation chimeras were generated from T and B cell-deficient mice (H-2(d) SCID or H-2(b) Rag-/-) and thymus-deficient nude mice (H-2(b) or H-2(d)). These tetraparental mice showed primary protective CD8(+) T cell responses, after lymphocytic choriomeningitis virus infection, that were peptide-specifically restricted to either thymic or nonthymic epithelial MHC at  ...[more]

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