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Disparate peptide‐dependent thymic selection outcomes in β2M‐deficient mice versus TAP‐1‐deficient mice: implications for repertoire formation
Author(s) -
Sasada Tetsuro,
Yang Yuting,
Lai CharChang,
Touma Maki,
Clayton Linda K.,
Liu Jinhuan,
Parisini Emilio,
Wang Jiahuai,
Reinherz Ellis L.
Publication year - 2003
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/immu.200310011
Subject(s) - biology , t cell receptor , avidity , peptide , negative selection , major histocompatibility complex , microbiology and biotechnology , immunology , genetically modified mouse , beta 2 microglobulin , transgene , endocrinology , medicine , antigen , t cell , biochemistry , gene , immune system , genome
Abstract Fetal thymic organ cultures of N15‐transgenic RAG‐2 –/– H‐2 b mice on normal, β‐2 microglobulin (β2M) –/– 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 β2M –/– mice but negatively selecting on TAP‐1 –/– or normal backgrounds. Very weak agonists and very weak antagonists are generally without effect in β2M –/– mice yet foster differentiation in TAP‐1 –/– animals. The 20–40‐fold reduction in β2M –/– thymic H‐2K b 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.