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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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Some IEk + MCC–reactive T cells from 99ATg mice react  with IEk + normal mouse peptides. T cell hybridomas specific for IEk +  MCC were prepared from 99ATg animals as described in Materials and  Methods and were assayed for their ability to respond to spleen cells from  various types of mice. The results shown are typical of two independent  experiments.
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Figure 4: Some IEk + MCC–reactive T cells from 99ATg mice react with IEk + normal mouse peptides. T cell hybridomas specific for IEk + MCC were prepared from 99ATg animals as described in Materials and Methods and were assayed for their ability to respond to spleen cells from various types of mice. The results shown are typical of two independent experiments.

Mentions: Hybridomas were tested for their ability to respond to B10.BR, IEwtTg Ii+, or 99ATg spleen cells. Examples of the reactivities of some of the hybridomas from 99ATg chimeric mice are shown in Fig. 4. None of the hybridomas responded to IEwtTg Ii+ or 99ATg cells. Thus the hybridomas were tolerant to class II proteins at the levels they were expressed in the chimeric mice. Several of the hybridomas did, however, respond to B10.BR spleen cells. Anti-IE addition to the stimulation cultures showed that this was due to reaction with IEk (data not shown). The parent T cells for these hybridomas must have been tolerant to IEk bound to the mouse peptides with which it is normally engaged at the very low levels at which it was expressed in the chimeric animals (Fig. 1), but were not tolerant to the same combination of IEk and peptides at the high levels at which it is expressed on B10.BR cells. These hybridomas were probably another example of the fact that selection on a particular MHC–peptide combination causes cells to mature, which are likely to react with that same MHC protein bound to other peptides, particularly when expressed at high levels (11–13).


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

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

Some IEk + MCC–reactive T cells from 99ATg mice react  with IEk + normal mouse peptides. T cell hybridomas specific for IEk +  MCC were prepared from 99ATg animals as described in Materials and  Methods and were assayed for their ability to respond to spleen cells from  various types of mice. The results shown are typical of two independent  experiments.
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Related In: Results  -  Collection

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

Figure 4: Some IEk + MCC–reactive T cells from 99ATg mice react with IEk + normal mouse peptides. T cell hybridomas specific for IEk + MCC were prepared from 99ATg animals as described in Materials and Methods and were assayed for their ability to respond to spleen cells from various types of mice. The results shown are typical of two independent experiments.
Mentions: Hybridomas were tested for their ability to respond to B10.BR, IEwtTg Ii+, or 99ATg spleen cells. Examples of the reactivities of some of the hybridomas from 99ATg chimeric mice are shown in Fig. 4. None of the hybridomas responded to IEwtTg Ii+ or 99ATg cells. Thus the hybridomas were tolerant to class II proteins at the levels they were expressed in the chimeric mice. Several of the hybridomas did, however, respond to B10.BR spleen cells. Anti-IE addition to the stimulation cultures showed that this was due to reaction with IEk (data not shown). The parent T cells for these hybridomas must have been tolerant to IEk bound to the mouse peptides with which it is normally engaged at the very low levels at which it was expressed in the chimeric animals (Fig. 1), but were not tolerant to the same combination of IEk and peptides at the high levels at which it is expressed on B10.BR cells. These hybridomas were probably another example of the fact that selection on a particular MHC–peptide combination causes cells to mature, which are likely to react with that same MHC protein bound to other peptides, particularly when expressed at high levels (11–13).

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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