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

  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},

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Thymic Origins of T Cell Receptor Alloreactivity.
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
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.
This finding implies that the degeneracy of positive selection for peptide ligands exceeds peptide-specific negative selection and is essential to increase the efficiency and diversity of the repertoire so that T cells with the same Ag specificity can be selected by different self MHC/ peptide complexes.
Inherent reactivity of unselected TCR repertoires to peptide-MHC molecules
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.
A quantitative theory of affinity-driven T cell repertoire selection.
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.
The Intricate Behavior of T Cells
Germline-encoded amino acids in the αβ T cell receptor control thymic selection
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.


Positive selection of CD4+ T cells by TCR ligation without aggregation even in the absence of MHC
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
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.
Unopposed positive selection and autoreactivity in mice expressing class II MHC only on thymic cortex
The keratin 14 (K14) promoter is used to re-express a class II MHC antigen (I-Ab) in class II-negative mice and autoreactive cells make up 5% of the peripheral CD4 T cells, providing an estimate of the minimal frequency of positively selected cells that must subsequently undergo negative selection for self-tolerance to be preserved.
Positive selection of thymocytes.
High frequency and nonrandom distribution of alloreactivity in T cell clones selected for recognition of foreign antigen in association with self class II molecules.
The high frequency of alloreactivity found in antigen-specific T cell clones is discussed, as well as the implications that the antigen-dependent skewing of the distribution ofAlloreactivity have for a one-receptor model vs a two-recept model of T cell recognition.
Molecular basis for the recognition of two structurally different major histocompatibility complex/peptide complexes by a single T-cell receptor.
The results strongly suggest that adaptation of the T-cell receptor to the different ligand structures, rather than molecular mimicry by the ligands, is the basis for the crossreactivity of 2C.
Control of MHC Restriction by TCR Vα CDR1 and CDR2
The germline-encoded Vα elements are a major influence on major histocompatibility class complex (MHC) restriction, most likely by a preferential interaction with one or the other class of MHC molecule.