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αβ T cell receptors as predictors of health and disease.

Attaf M, Huseby E, Sewell AK - Cell. Mol. Immunol. (2015)

Bottom Line: However, a number of immune responses are associated with the selection of predictable, narrow, or skewed repertoires and public TCR chains.Here, we summarize the current knowledge on the formation of the TCR repertoire and its maintenance in health and disease.We also outline the various molecular mechanisms that govern the composition of the pre-selection, naive and antigen-specific TCR repertoires.

View Article: PubMed Central - PubMed

Affiliation: Cardiff University School of Medicine, Cardiff, UK.

ABSTRACT
The diversity of antigen receptors and the specificity it underlies are the hallmarks of the cellular arm of the adaptive immune system. T and B lymphocytes are indeed truly unique in their ability to generate receptors capable of recognizing virtually any pathogen. It has been known for several decades that T lymphocytes recognize short peptides derived from degraded proteins presented by major histocompatibility complex (MHC) molecules at the cell surface. Interaction between peptide-MHC (pMHC) and the T cell receptor (TCR) is central to both thymic selection and peripheral antigen recognition. It is widely assumed that TCR diversity is required, or at least highly desirable, to provide sufficient immune coverage. However, a number of immune responses are associated with the selection of predictable, narrow, or skewed repertoires and public TCR chains. Here, we summarize the current knowledge on the formation of the TCR repertoire and its maintenance in health and disease. We also outline the various molecular mechanisms that govern the composition of the pre-selection, naive and antigen-specific TCR repertoires. Finally, we suggest that with the development of high-throughput sequencing, common TCR 'signatures' raised against specific antigens could provide important diagnostic biomarkers and surrogate predictors of disease onset, progression and outcome.

No MeSH data available.


Related in: MedlinePlus

Size and composition of the pre-selection, naive and antigen-experienced repertoires. TCR diversity is greatest in the pre-selection repertoire (gray). Positive and negative selection in the thymus purges the pre-selection repertoire of most specificities, creating a peripheral naive repertoire that is substantially less diverse (green). In the periphery, antigen exposure further narrows the repertoire over time leading to clonal expansion of antigen-specific populations (blue). TCR diversity is largely preserved throughout the human lifespan, except in infancy and old age, but the net distribution of TCR clonotypes is altered. TCR, T cell receptor.
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fig3: Size and composition of the pre-selection, naive and antigen-experienced repertoires. TCR diversity is greatest in the pre-selection repertoire (gray). Positive and negative selection in the thymus purges the pre-selection repertoire of most specificities, creating a peripheral naive repertoire that is substantially less diverse (green). In the periphery, antigen exposure further narrows the repertoire over time leading to clonal expansion of antigen-specific populations (blue). TCR diversity is largely preserved throughout the human lifespan, except in infancy and old age, but the net distribution of TCR clonotypes is altered. TCR, T cell receptor.

Mentions: Successfully rearranged TCRs are expressed at the T cell surface and audition for selection on thymic self-pMHC ligands. The net result of thymic selection is that the post-selection repertoire is largely purged of most clonotypes.23 Typically, only one in a hundred thymocytes are thought to be granted access to the periphery24 (Figure 3). Assessing the relative distribution of TCR clonotypes has long been a challenge in the naive pool because of low precursor frequency. Nevertheless, identifying the factors that shape the composition of the naive repertoire is critical to our understanding of protective T cell-mediated immunity because naive lymphocytes represent the precursor pool from which all immune responses arise.


αβ T cell receptors as predictors of health and disease.

Attaf M, Huseby E, Sewell AK - Cell. Mol. Immunol. (2015)

Size and composition of the pre-selection, naive and antigen-experienced repertoires. TCR diversity is greatest in the pre-selection repertoire (gray). Positive and negative selection in the thymus purges the pre-selection repertoire of most specificities, creating a peripheral naive repertoire that is substantially less diverse (green). In the periphery, antigen exposure further narrows the repertoire over time leading to clonal expansion of antigen-specific populations (blue). TCR diversity is largely preserved throughout the human lifespan, except in infancy and old age, but the net distribution of TCR clonotypes is altered. TCR, T cell receptor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496535&req=5

fig3: Size and composition of the pre-selection, naive and antigen-experienced repertoires. TCR diversity is greatest in the pre-selection repertoire (gray). Positive and negative selection in the thymus purges the pre-selection repertoire of most specificities, creating a peripheral naive repertoire that is substantially less diverse (green). In the periphery, antigen exposure further narrows the repertoire over time leading to clonal expansion of antigen-specific populations (blue). TCR diversity is largely preserved throughout the human lifespan, except in infancy and old age, but the net distribution of TCR clonotypes is altered. TCR, T cell receptor.
Mentions: Successfully rearranged TCRs are expressed at the T cell surface and audition for selection on thymic self-pMHC ligands. The net result of thymic selection is that the post-selection repertoire is largely purged of most clonotypes.23 Typically, only one in a hundred thymocytes are thought to be granted access to the periphery24 (Figure 3). Assessing the relative distribution of TCR clonotypes has long been a challenge in the naive pool because of low precursor frequency. Nevertheless, identifying the factors that shape the composition of the naive repertoire is critical to our understanding of protective T cell-mediated immunity because naive lymphocytes represent the precursor pool from which all immune responses arise.

Bottom Line: However, a number of immune responses are associated with the selection of predictable, narrow, or skewed repertoires and public TCR chains.Here, we summarize the current knowledge on the formation of the TCR repertoire and its maintenance in health and disease.We also outline the various molecular mechanisms that govern the composition of the pre-selection, naive and antigen-specific TCR repertoires.

View Article: PubMed Central - PubMed

Affiliation: Cardiff University School of Medicine, Cardiff, UK.

ABSTRACT
The diversity of antigen receptors and the specificity it underlies are the hallmarks of the cellular arm of the adaptive immune system. T and B lymphocytes are indeed truly unique in their ability to generate receptors capable of recognizing virtually any pathogen. It has been known for several decades that T lymphocytes recognize short peptides derived from degraded proteins presented by major histocompatibility complex (MHC) molecules at the cell surface. Interaction between peptide-MHC (pMHC) and the T cell receptor (TCR) is central to both thymic selection and peripheral antigen recognition. It is widely assumed that TCR diversity is required, or at least highly desirable, to provide sufficient immune coverage. However, a number of immune responses are associated with the selection of predictable, narrow, or skewed repertoires and public TCR chains. Here, we summarize the current knowledge on the formation of the TCR repertoire and its maintenance in health and disease. We also outline the various molecular mechanisms that govern the composition of the pre-selection, naive and antigen-specific TCR repertoires. Finally, we suggest that with the development of high-throughput sequencing, common TCR 'signatures' raised against specific antigens could provide important diagnostic biomarkers and surrogate predictors of disease onset, progression and outcome.

No MeSH data available.


Related in: MedlinePlus