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第十三届全国免疫学学术大会

作者： Peng Wu Rui Qin Danmei Yao Tongtong Zhang Wei Hu Chenyi An Junwei Liu Jizhong Lou Wei Chen Institute of Neuroscience School of of MedicineZhejiang University Key Laboratory of RNA Biology Institute of BiophysicsChinese Academy of Sciences

CD8 T cells use TCRs to specially recognize foreign-pMHCs which activates TCR downstream signals and initiates adaptive immunity. CD8 s work as co-receptors to stabilize TCR-pMHC-I interactions and amplify TCR signals. Recently, we found that mechanical force can induce conformational changes of MHC-I and prolong TCR-pMHC bond lifetime to form antigen specific catch bonds which enhance the potency of TCR antigen recognition and T cell activation. We hypothesize that mechanical force may regulate CD8 engagement with MHC-I to enhance CD8 biological functions on the other hand CD8 may also enhance the mechanical-chemical regulation of TCR antigen recognition. To test these hypotheses, we integrate single molecule force spectroscopy, molecular dynamic(MD) simulation and T-cell functional assays to study the detailed mechanism of mechanical-chemical regulation of CD8 enhancement. We found that mechanical force can rapidly(antigen recognition. Our findings provide new insights and basic theory to advance our understanding of mechano-immunology and to potentially benefit clinical immunotherapy.

关键词： CD8 TCR-pMHC catch bond mechanical-chemical regulation antigen recognition

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Diversity of yO T-cell antigens

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Cellular & Molecular Immunology 2013年第1期10卷 13-20页

作者： Willi K Born M Kemal Aydintug Rebecca L O'Brien Integrated Department of Immunology National Jewish Health Denver CO USA University of Colorado Denver Aurora CO USACorrespondence: Dr WK Born National Jewish Health 1400 Jackson Street GB K409 Denver CO 80206 USA.

In the last two decades, it has become clear that yo T cells recognize a diverse array of antigens including self and foreign, large and small, and peptidic and non-peptidic molecules. In this respect, 78 antigens as a whole resemble more the antigens recognized by antibodies than those recognized by T cells. Because of this antigenic diversity, no single mechanism--such as the major histocompatibility complex （MHC） restriction of ap T cells--is likely to provide a basis for all observed T-cell antigen receptor （TCR）-dependent 78 T-cell responses. Furthermore, available evidence suggests that many individual 78 T cells are poly-specific, probably using different modes of ligand recognition in their responses to unrelated antigens. While posing a unique challenge in the maintenance of self-tolerance, this broad reactivity pattern might enable multiple overlapping uses of 78 T-cell populations, and thus generate a more efficient immune response.

关键词： antigen recognition ligand T-cell receptor yo T cells

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3efining the nature of human yo T cells： a biographical ketch of the highly empathetic

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Cellular & Molecular Immunology 2013年第1期10卷 21-29页

作者： Shirin Kalyan Dieter Kabelitz Institute of Immunology Christian-Albrechts University K)el Kiel Germany

The elusive task of defining the character of 76 T cells has been an evolving process for immunologists since stumbling upon their existence during the molecular characterization of the a and p T cell receptor genes of their better understood brethren. Defying the categorical rules used to distinctly characterize lymphocytes as either innate or adaptive in nature, 76 T cells inhabit a hybrid world of their own. At opposing ends of the simplified spectrum of modes of antigen recognition used by lymphocytes, natural killer and ap T cells are particularly well equipped to respond to the ＇missing self＇ and the ＇dangerous non-self＇, respectively. However, between these two reductive extremes, we are chronically faced with the challenge of making peace with the ＇safe non-self＇ and dealing with the inevitable ＇distressed self＇, and it is within this more complex realm 76 T cells excel thanks to their highly empathetic nature. This review gives an overview of the latest insights revealing the unfolding story of human 76 T cells, providing a biographical sketch of these unique lymphocytes in an attempt to capture the essence of their fundamental nature and events that influence their life trajectory. What hangs in their balance is their nuanced ability to differentiate the friends from the foe and the pathological from the benign to help us adapt swiftly and efficiently to life＇s many stresses.

关键词： antigen recognition danger-associated molecular patterns gamma delta T cell subsets immune homeostasis innateimmunity stress response

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Regulation of T cell receptor signaling by lipid metabolites

Regulation of T cell receptor signaling by lipid metabolites

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第十四届全国免疫学学术大会

作者： Feng Wang Shanghai Jiao Tong University School of Medicine

Most adaptive immune responses require the activation of specific T cells through the T cell receptor-CD3 complex(TCR). Previously, we found that cholesterol sulfate(CS), a naturally-occurring cholesterol metabolite, inhibits CD3 ITAM phosphorylation, a crucial first step in T cell activation. CS deficient mice exhibit a heightened sensitivity to a self-antigen during thymocyte development. Here we show that besides disrupting TCR multimers, CS can also regulate the conformation of TCR-CD3 leading to a change in the secondary structure of CD3 cytoplasmic domains to block TCR signaling. Our Results demonstrate that membrane CS bridges the gap between two fundamental TCR signaling models(clustering and conformational change). This novel regulatory role of metabolite highlights the importance of the membrane microenvironment in modulating cell surface receptor activation. Moreover, our finding provides an opportunity to preform functional engineering on the TCR-CD3 complex for enhancing the ability of antigen recognition and boosting anti-tumor immunity of T cell.

关键词： T cell receptor lipid metabolite cholesterol sulfate antigen recognition anti-tumor immunity

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