Novel MHC-Independent αßTCRs Specific for CD48, CD102, and CD155 Self-Proteins and Their Selection in the Thymus.
Front Immunol
; 11: 1216, 2020.
Article
em En
| MEDLINE
| ID: mdl-32612609
ABSTRACT
MHC-independent αßTCRs (TCRs) recognize conformational epitopes on native self-proteins and arise in mice lacking both MHC and CD4/CD8 coreceptor proteins. Although naturally generated in the thymus, these TCRs resemble re-engineered therapeutic chimeric antigen receptor (CAR) T cells in their specificity for MHC-independent ligands. Here we identify naturally arising MHC-independent TCRs reactive to three native self-proteins (CD48, CD102, and CD155) involved in cell adhesion. We report that naturally arising MHC-independent TCRs require high affinity TCR-ligand engagements in the thymus to signal positive selection and that high affinity positive selection generates a peripheral TCR repertoire with limited diversity and increased self-reactivity. We conclude that the affinity of TCR-ligand engagements required to signal positive selection in the thymus inversely determines the diversity and self-tolerance of the mature TCR repertoire that is selected.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Timo
/
Subpopulações de Linfócitos T
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Receptores de Antígenos de Linfócitos T alfa-beta
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Tolerância a Antígenos Próprios
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Especificidade do Receptor de Antígeno de Linfócitos T
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Seleção Clonal Mediada por Antígeno
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Complexo Principal de Histocompatibilidade
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Front Immunol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos