1 / 24

Ligand for allogeneic T-cell recognition and its potential applications

Ligand for allogeneic T-cell recognition and its potential applications. Xiongwen Wu Dept. of Immunology Tongji Medical College, the HUST Wuhan, China. Ligand for T cell recognition - pMHC. Multimerized pMHC is able to bind to TCR with high affinity. pMHC dimer ：

seda
Télécharger la présentation

Ligand for allogeneic T-cell recognition and its potential applications

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Ligand for allogeneic T-cell recognition and its potential applications Xiongwen Wu Dept. of Immunology Tongji Medical College, the HUST Wuhan, China

  2. Ligand for T cell recognition - pMHC

  3. Multimerized pMHC is able to bind to TCR with high affinity • pMHC dimer： • Promote or inhibite antigen-specific allogeneic T cells • pMHC tetramer： Detect antigen-specific T cells 图1. pMHC四聚体结构示意图 图2. pMHC二聚体结构示意图

  4. pMHC dimer：promotion or inhibition of antigen-specific allogeneic T cells 1. Antigen-specific inhibition Soluble pMHC dimer binds to TCR without co-stimulatory signal 2. Antigen-specific promotion Cell membrane-bound pMHC dimer raise allo-restricted peptide-specific T cells

  5. Cumulative effect of T cells specific to each peptide epitope could account for the strength and diversity of the allo-response • Xiufang Weng, Zhihui Liang, Xiaoling Lu, Maohua Zhong, Shengjun Lu, Caie Zhang, Jing Deng, Xiongwen Wu*, Feili Gong.Peptide-specific, allogeneic T cell response in vitro induced by a self-peptide binding to HLA-A2.Sci China Ser C-Life Sci. 2007, 50:203-211 Many studies show that allogeneic T-cell responses like syngeneic T-cell responses, are largely peptide-specific

  6. 1. Antigen-specific inhibition Peptide/HLA-A2 dimer inhibits undesired T-cell response

  7. Soluble pMHC dimer inhibits T-cell allo-response in MLC 图7. 可溶性pMHC二聚体诱导特异性的同种T细胞耐受的示意图

  8. Inhibition effect of Tyr/HLA-A2 dimer on T-cell proliferation in MLC is pMHC-specific a, HLA-A2-ve PBLs b, HLA-A2-ve PBLs & T2/Tyr c, b + Tyr368-376 peptide d, b + HIV/HLA-A2 dimer e, b + Tyr/HLA-A2 dimer T2/Tyr: T2 pulsed with Tyr

  9. Inhibition effect of Tyr/HLA-A2 dimer on T-cell proliferation in MLC • Tyr/HLA-A2 dimer in 2nM seems to reach the maximum inhibition • thereverse of the inhibition effect of Tyr/HLA-A2 dimer by HLA-A2-specific mAb BB7.2 • Xiufang Weng, Maohua Zhong, Zhihui Liang, Shengjun Lu, Xueling Chen, Janan Li, Juan Hao, Feili Gong, Xiongwen Wu*.Peptide-dependent inhibition of alloreactive T-cell response by soluble divalent HLA-A2/IgG molecule in vitro.Transplantation. 2007, 84(10):1298-306.

  10. CD8lowCD28- T cells: a human CD8 Ts subset with alloantigen specificity induced by soluble HLA-A2 dimer in vitro

  11. The dimer-expanded CD8lowCD28- T cells exhibit suppression on allo-reactive T cells

  12. The CD8lowCD28- T cells exhibit alloantigen-specific suppression which requires cell-cell contact

  13. Elevated membrane-bound TGF-β1 expression is involved in suppression of the CD8lowCD28‑ T cells

  14. The frequency of CD8lowCD28- T cells is positively associated with plasma levels of soluble HLA class I in human peripheral blood

  15. 2. Antigen-specific promotion generation of allo-restricted peptide-specific T cells exploiting T-cell repertoire of MHC mismatched individuals to circumvent tumor or virus tolerance Xiufang Weng, Xiongwen Wu*, Allo-restricted CTLs generated by co-culture of PBLs and autologous monocytes loaded with allogeneic peptide/HLA/IgG1-Fc fusion protein.Journal of Leukocyte Biology, 2009;85(3):574-81. Xueling Chen, Xiongwen Wu*, Raising allo-restricted CTLs by co-culture of murine splenocytes with autologous macrophage bearing the peptide/allo-MHC complex.Human Immunology, 2009; 70(2):79-84 Song Y, Sun W, Weng X, Liang Z, Yu Q, Wang Z, Ouyang L, Chen J, Wu X, Shen G, Wu X. Tumor rejection effects of allo-restricted tumor peptide-specific CD4⁺ T cells on human cervical cancer cell xenograft in nude mice. Cell Transplant. 2012 Apr 20. [Epub ahead of print]

  16. Tumor rejection effects of allo-restricted tumor peptide-specific CD4+ T cells on human cervical cancer cell xenograft in nude mice

  17. Preparation of the HLA-DR15/IgG1-Fc fusion protein and its binding to HLA-DR15-ve monocyte

  18. CD4+ T cell proliferation & CD4+ Th1 cell induction in co-culturing

  19. allo-restricted and peptide-specific properties of the expanded CD4+ T cells

  20. Tumor rejection effects of allo-restricted E7-specific CD4+T cells on human cervical cancer cell xenografts in nude mice

  21. Research Proposal 03-2002 Allo-reactive T cells comprise various peptide specific T cell clones

  22. Summary • Allogeneic T-cell responses, as syngeneic T-cell responses, are largely pMHC-specific • Soluble pMHC dimer can inhibit T-cell response in an antigen-specific manner • Membrane-associated pMHC dimer is able to raise allo-restricted peptide-specific T cells

  23. Our Team

  24. 致 谢 Thanks

More Related