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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.

Show MeSH
IEk + MCC–specific T cells from 99ATg mice are as reactive with their ligand as T cells from normal mice are. The response of  99ATg T cell hybridomas to IEk + MCC was compared with that of a  representative T cell hybridoma, 5KC-73.8/S1.6, from normal mice. The  results shown are typical of two independent experiments.
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Figure 5: IEk + MCC–specific T cells from 99ATg mice are as reactive with their ligand as T cells from normal mice are. The response of 99ATg T cell hybridomas to IEk + MCC was compared with that of a representative T cell hybridoma, 5KC-73.8/S1.6, from normal mice. The results shown are typical of two independent experiments.

Mentions: The hybridomas were also tested for their ability to respond to different concentrations of MCC presented by B10.BR cells (Fig. 5). Many of the hybridomas responded well to this antigen and were as sensitive to low doses of the peptide as a typical hybridoma prepared from primed T cells from a normal mouse. Some of the hybridomas, for example KMAC-92, which responded to B10.BR cells in the absence of peptide responded better when increasing doses of MCC were added to the cultures.


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 + MCC–specific T cells from 99ATg mice are as reactive with their ligand as T cells from normal mice are. The response of  99ATg T cell hybridomas to IEk + MCC was compared with that of a  representative T cell hybridoma, 5KC-73.8/S1.6, from normal mice. The  results shown are typical of two independent experiments.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: IEk + MCC–specific T cells from 99ATg mice are as reactive with their ligand as T cells from normal mice are. The response of 99ATg T cell hybridomas to IEk + MCC was compared with that of a representative T cell hybridoma, 5KC-73.8/S1.6, from normal mice. The results shown are typical of two independent experiments.
Mentions: The hybridomas were also tested for their ability to respond to different concentrations of MCC presented by B10.BR cells (Fig. 5). Many of the hybridomas responded well to this antigen and were as sensitive to low doses of the peptide as a typical hybridoma prepared from primed T cells from a normal mouse. Some of the hybridomas, for example KMAC-92, which responded to B10.BR cells in the absence of peptide responded better when increasing doses of MCC were added to the cultures.

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