Fetal thymic organ cultures of N15-transgenic RAG-2(-/-) H-2(b) mice on normal, beta-2 microglobulin (beta2M)(-/-) or transporter associated with antigen processing (TAP-1)(-/-) MHCI-deficient backgrounds were used to examine differentiation of thymocytes bearing a TCR specific for a viral peptide bound to H-2K(b). Strong agonists mediate negative selection in all mice whereas weak agonists are positively selecting in beta2M(-/-) mice but negatively selecting on TAP-1(-/-) or normal backgrounds. Very weak agonists and very weak antagonists are generally without effect in beta2M(-/-) mice yet foster differentiation in TAP-1(-/-) animals. The 20-40-fold reduction in beta2M(-/-) thymic H-2Kb surface expression suggests that the avidity of the TCR for peptide-MHCI accounts for these differences, consistent with effects of TCR density and individual thymic-peptide abundance in peptide-MHC complexes. TCR-self-MHC interaction dominates K-b-based selection, subtly modulated by peptides as revealed by X-ray crystallography.
Sasada, T., Yang, Y., Lai, C., Touma, M., Clayton, L.K., Liu, J., et al. (2003). Disparate peptide-dependent thymic selection outcomes in beta2M-deficient mice versus TAP-1-deficient mice: implications for repertoire formation. EUROPEAN JOURNAL OF IMMUNOLOGY, 33(2), 368-380 [10.1002/immu.200310011].
Disparate peptide-dependent thymic selection outcomes in beta2M-deficient mice versus TAP-1-deficient mice: implications for repertoire formation
Parisini, Emilio;
2003
Abstract
Fetal thymic organ cultures of N15-transgenic RAG-2(-/-) H-2(b) mice on normal, beta-2 microglobulin (beta2M)(-/-) or transporter associated with antigen processing (TAP-1)(-/-) MHCI-deficient backgrounds were used to examine differentiation of thymocytes bearing a TCR specific for a viral peptide bound to H-2K(b). Strong agonists mediate negative selection in all mice whereas weak agonists are positively selecting in beta2M(-/-) mice but negatively selecting on TAP-1(-/-) or normal backgrounds. Very weak agonists and very weak antagonists are generally without effect in beta2M(-/-) mice yet foster differentiation in TAP-1(-/-) animals. The 20-40-fold reduction in beta2M(-/-) thymic H-2Kb surface expression suggests that the avidity of the TCR for peptide-MHCI accounts for these differences, consistent with effects of TCR density and individual thymic-peptide abundance in peptide-MHC complexes. TCR-self-MHC interaction dominates K-b-based selection, subtly modulated by peptides as revealed by X-ray crystallography.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.