The MHC Reactivity of the T Cell Repertoire Prior to Positive and Negative Selection

@article{Zerrahn1997TheMR,
  title={The MHC Reactivity of the T Cell Repertoire Prior to Positive and Negative Selection},
  author={Jens Erik Zerrahn and Werner Held and David H. Raulet},
  journal={Cell},
  year={1997},
  volume={88},
  pages={627-636}
}
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344 Citations

How the T Cell Repertoire Becomes Peptide and MHC Specific
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Assessment of the preselection of TCR repertoire, molecular evidence for the germline encoded TCR bias for MHC, and for the coreceptor sequestration model in the context of alloreactivity and transplantation are discussed.
Negative selection imparts peptide specificity to the mature T cell repertoire
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It is shown that the development of peptide-specific T cells is not intrinsic to thymocytes that undergo thymic-positive selection but is an outcome of eliminating, through negative selection, thymocyte bearing TCRs with extensive peptide cross-reactivity.
In the normal repertoire of CD4+ T cells, a single class II MHC/peptide complex positively selects TCRs with various antigen specificities.
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Inherent reactivity of unselected TCR repertoires to peptide-MHC molecules
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It is shown that TCRs have intrinsic specificity for MHC molecules, inherent to TCRαβ sequences, and enhanced but not determined by coreceptor expression, which is further strengthened in the presence of coreceptors.
MHC restriction is imposed on a diverse T cell receptor repertoire by CD4 and CD8 co-receptors during thymic selection.
A quantitative theory of affinity-driven T cell repertoire selection.
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The role of the MHC and peptide contribution to TCR binding is analysed, and it is found that their relative, rather than absolute value, is important in shaping the mature repertoire.
Role of thymic cortex-specific self-peptides in positive selection of T cells.
The Intricate Behavior of T Cells
Germline-encoded amino acids in the αβ T cell receptor control thymic selection
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Results show that thymic selection is controlled by germline-encoded MHC contact points in the αβ TCR and indicate that the diversity of the peripheral T-cell repertoire is enhanced by this ‘built-in’ specificity.
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References

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Positive selection of CD4+ T cells by TCR ligation without aggregation even in the absence of MHC
TLDR
It is reported that direct ligation of TCR molecules by monoclonal antibodies specific for either clonotypic or CD3 chains can signal immature thymocytes to differentiate into mature CD4+8− T cells, even in the absence of MHC expression and MHC-dependent CD4 coreceptor signalling.
T cell receptor interaction with peptide/major histocompatibility complex (MHC) and superantigen/MHC ligands is dominated by antigen
TLDR
Comparing the responses of T cells bearing structurally related TCRs to cytochrome c peptides and staphylococcal enterotoxin A presented by 13 mutant antigen-presenting cell (APC) lines suggests a molecular basis for recent reports in which either peptide analogues or superantigens trigger distinct pathways of T cell activation.
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TLDR
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TLDR
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