[논문]Diversity of T cell repertoire shaped by a single peptide ligand is critically affected by its amino acid residue at a T cell receptor contact

Fukui, Yoshinori; Oono, Takamasa; Cabaniols, Jean-Pierre; Nakao, Kazuki; Hirokawa, Katsuiku; Inayoshi, Ayumi; Sanui, Terukazu; Kanellopoulos, Jean; Iwata, Eiko; Noda, Mayuko; Katsuki, Motoya; Kourilsky, Philippe; Sasazuki, Takehiko

doi:10.1073/pnas.250470797

[해외논문] Diversity of T cell repertoire shaped by a single peptide ligand is critically affected by its amino acid residue at a T cell receptor contact 원문보기

Proceedings of the National Academy of Sciences of the United States of America, v.97 no.25, 2000년, pp.13760 - 13765

Fukui, Yoshinori (Department of Genetics, CREST (Core Research for Evolutional Science and Technology), Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan) , Oono, Takamasa (Laboratoire de Biologie Molé) , Cabaniols, Jean-Pierre (culaire du Gè) , Nakao, Kazuki (ne, Institut Pasteur, 75724 Paris, France) , Hirokawa, Katsuiku (Department of DNA Biology and Embryo Engineering, Institute of Medical Science, Tokyo University, Tokyo 108, Japan) , Inayoshi, Ayumi (and Department of Pathology and Immunology, Tokyo Medical and Dental University, Tokyo 113, Japan) , Sanui, Terukazu (Department of Genetics, CREST (Core Research for Evolutional Science and Technology), Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan) , Kanellopoulos, Jean (Laboratoire de Biologie Molé) , Iwata, Eiko (culaire du Gè) , Noda, Mayuko (ne, Institut Pasteur, 75724 Paris, France) , Katsuki, Motoya (Department of DNA Biology and Embryo Engineering, Institute of Medical Science, Tokyo University, Tokyo 108, Japan) , Kourilsky, Philippe (and Department of Pathology and Immunology, Tokyo Medical and Dental University, Tokyo 113, Japan) , Sasazuki, Takehiko (Department of Genetics, CREST (Core Rese)

Abstract ▼ AI-Helper

T cell differentiation in the thymus is driven by positive selection through the interaction of αβ T cell receptors (TCRs) with self-peptides bound to self-major histocompatibility complex molecules, yet the influence of the peptide sequence on this process remains unknown. To address this issue, we have compared CD4+T cell differentiation between two sets of mouse lines in which MHC class II I-Abmolecules are occupied with either Eα chain-derived peptide (pEα) or its variant,p60K, with one amino acid substitution from leucine to lysine at P5 residue of TCR contacts. Here, we show that despite the comparable expression of I-Ab-peptide complex in the thymus, this substitution from leucine to lysine affects efficiency of positive selection, resulting in extremely small numbers of CD4+T cells to be selected to mature on I-Ab-p60K complex. Furthermore, we show that, although I-Ab-pEα complex selects diverse T cells, T cell repertoire shaped by I-Ab-p60K complex is markedly constrained. Our findings thus suggest that positive selection is both specific and degenerate, depending on the amino acid residues at TCR contacts of the selecting self-peptides.

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[해외논문] Diversity of T cell repertoire shaped by a single peptide ligand is critically affected by its amino acid residue at a T cell receptor contact 원문보기

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