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Selection of antigen-specific T cells by a single IEk peptide combination.

Liu CP, Parker D, Kappler J, Marrack P - J. Exp. Med. (1997)

Bottom Line: Some of the TCRs on the selected T cells were related to those on cells from normal mice and some were not.IEk bound to the Hb variant, on the other hand, did not select any T cells which could react with IEk + MCC.These results demonstrate that although positive selection is a partially degenerate event, the sequence of the peptide involved in positive selection controls the selected repertoire.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.

ABSTRACT
In normal mice, major histocompatibility complex (MHC) proteins are bound to many different peptides, derived from the proteins of their host. In the thymus, the diversity of this collection of MHC + peptide ligands allows thymocytes bearing many different T cell receptors (TCRs) to mature by low avidity reactions between the MHC + peptide ligands and the thymocyte TCRs. To investigate this problem, the selection of T cells specific for a well-studied combination of MHC + peptide, IEk + moth cytochrome c 88-103 (MCC), was investigated. Mice were created that expressed IEk bound to a single peptide, either a variant of MCC in which a critical TCR contact residue, 99K, was changed to A, or a variant of a mouse hemoglobin 64-76 (Hb) peptide, 72A. IEk bound to the MCC variant caused the clonal deletion of some T cells specific for the IEk + MCC ligand; nevertheless, it also positively selected many T cells that could react with this ligand. Some of the TCRs on the selected T cells were related to those on cells from normal mice and some were not. IEk bound to the Hb variant, on the other hand, did not select any T cells which could react with IEk + MCC. These results demonstrate that although positive selection is a partially degenerate event, the sequence of the peptide involved in positive selection controls the selected repertoire.

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IEk-99A causes the clonal deletion of T cells bearing canonical IEk + MCC–reactive TCRs. Animals expressing the AND or AD10  TCR transgenes were crossed with 72ATg or 99ATg mice, and the animals were intercrossed such that some were H2fxk and others were H2f  homozygous. Thymocytes from these animals were stained with anti-Vα11, anti-Vβ3, and CD4. The counts are those of cells/thymus-bearing  CD4 and high levels of Vα11 and Vβ3. The results shown are the averages of between one and three mice of each type.
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Figure 3: IEk-99A causes the clonal deletion of T cells bearing canonical IEk + MCC–reactive TCRs. Animals expressing the AND or AD10 TCR transgenes were crossed with 72ATg or 99ATg mice, and the animals were intercrossed such that some were H2fxk and others were H2f homozygous. Thymocytes from these animals were stained with anti-Vα11, anti-Vβ3, and CD4. The counts are those of cells/thymus-bearing CD4 and high levels of Vα11 and Vβ3. The results shown are the averages of between one and three mice of each type.

Mentions: The results in Fig. 3 show that CD4+ thymocytes bearing either of the two transgenes were selected with low efficiency in nontransgenic H2f homozygous mice. This was not because H2f proteins caused deletion of thymocytes bearing these TCRs since CD4+ thymocytes bearing either the AND or AD10 TCRs appeared in large numbers in H2fxk mice, positively selected by the wild-type IEk protein + some unknown mouse peptide.


Selection of antigen-specific T cells by a single IEk peptide combination.

Liu CP, Parker D, Kappler J, Marrack P - J. Exp. Med. (1997)

IEk-99A causes the clonal deletion of T cells bearing canonical IEk + MCC–reactive TCRs. Animals expressing the AND or AD10  TCR transgenes were crossed with 72ATg or 99ATg mice, and the animals were intercrossed such that some were H2fxk and others were H2f  homozygous. Thymocytes from these animals were stained with anti-Vα11, anti-Vβ3, and CD4. The counts are those of cells/thymus-bearing  CD4 and high levels of Vα11 and Vβ3. The results shown are the averages of between one and three mice of each type.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199109&req=5

Figure 3: IEk-99A causes the clonal deletion of T cells bearing canonical IEk + MCC–reactive TCRs. Animals expressing the AND or AD10 TCR transgenes were crossed with 72ATg or 99ATg mice, and the animals were intercrossed such that some were H2fxk and others were H2f homozygous. Thymocytes from these animals were stained with anti-Vα11, anti-Vβ3, and CD4. The counts are those of cells/thymus-bearing CD4 and high levels of Vα11 and Vβ3. The results shown are the averages of between one and three mice of each type.
Mentions: The results in Fig. 3 show that CD4+ thymocytes bearing either of the two transgenes were selected with low efficiency in nontransgenic H2f homozygous mice. This was not because H2f proteins caused deletion of thymocytes bearing these TCRs since CD4+ thymocytes bearing either the AND or AD10 TCRs appeared in large numbers in H2fxk mice, positively selected by the wild-type IEk protein + some unknown mouse peptide.

Bottom Line: Some of the TCRs on the selected T cells were related to those on cells from normal mice and some were not.IEk bound to the Hb variant, on the other hand, did not select any T cells which could react with IEk + MCC.These results demonstrate that although positive selection is a partially degenerate event, the sequence of the peptide involved in positive selection controls the selected repertoire.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.

ABSTRACT
In normal mice, major histocompatibility complex (MHC) proteins are bound to many different peptides, derived from the proteins of their host. In the thymus, the diversity of this collection of MHC + peptide ligands allows thymocytes bearing many different T cell receptors (TCRs) to mature by low avidity reactions between the MHC + peptide ligands and the thymocyte TCRs. To investigate this problem, the selection of T cells specific for a well-studied combination of MHC + peptide, IEk + moth cytochrome c 88-103 (MCC), was investigated. Mice were created that expressed IEk bound to a single peptide, either a variant of MCC in which a critical TCR contact residue, 99K, was changed to A, or a variant of a mouse hemoglobin 64-76 (Hb) peptide, 72A. IEk bound to the MCC variant caused the clonal deletion of some T cells specific for the IEk + MCC ligand; nevertheless, it also positively selected many T cells that could react with this ligand. Some of the TCRs on the selected T cells were related to those on cells from normal mice and some were not. IEk bound to the Hb variant, on the other hand, did not select any T cells which could react with IEk + MCC. These results demonstrate that although positive selection is a partially degenerate event, the sequence of the peptide involved in positive selection controls the selected repertoire.

Show MeSH
Related in: MedlinePlus