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Yu Lab
Principal Investigator: Xu Yu Link: Acute HIV Infection Research Program
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Dr Yu’s laboratory focuses on three different aspects of HIV-1 pathogenesis:
| 1. | The investigation of TCR recruitment and TCR signaling pathways in HIV-1-specific T cells. These studies aim at determining how specific recruitment of TCRs in HIV-1-specific CD8+ T cells contribute to the shaping of HIV-1 viral sequence evolution and at understanding how clonotype composition and TCR signaling mechanisms in HIV-1-specific T cells contribute to their functionality and antiviral efficacy. | |
| 2. | The analysis of immunoregulatory mechanisms and pathways that have a critical impact on the evolution and functionality of adaptive and innate immune responses against HIV-1. These investigations are centered on the analysis of immune receptors on dendritic cells that determine the functional profile of these cells either in an inhibitory or a stimulatory way. Recent studies in Dr. Yu’s unfolded a dynamic interplay between these receptors and HIV-1 CTL epitope/MHC class I complexes, suggesting that CTL epitopes have, in addition to their role as immunogens for the induction of HIV-1-specific CD8+ T cells responses, an important immunoregulatory function that is mediated by specific binding interactions with these receptors. These investigations ultimately aim at developing strategies for the manipulation of these immunoregulatory pathways in immunological treatment approaches against HIV-1. | |
| 3. | The investigation of cells and tissue compartments that serve as the reservoir for latent and productive HIV-1 infection and how host restriction factors impact on the formation of these reservoirs. Dr. Yu’s lab is approaching these questions by developing innovative new techniques to specifically identify the individual cells that represent the latent reservoir for HIV-1 and by analyzing host restriction factors that influence specific viral replication dynamics and clinical patterns of HIV-1 disease progression. | |
| Important Accomplishments: | ||
| 1. | First identification of public TCR recruitment patterns in HIV-1-specific CD8+ T cells and their influence on viral escape mechanisms. | |
| 2. | The first longitudinal analysis of TCR clonotype evolution in HIV-1-specific CD8+ T cells after primary HIV-1 infection and its impact on T cell functionality and HIV-1 disease progression. | |
| 3. | First description of a viral CTL epitope mutation that alters recognition of peptide/MHC class I complexes by inhibitory myelomonocytic MHC class I receptors on dendritic cells. This suggests that HIV-1 sequence variations can specifically change functional properties of dendritic cells. | |
| 4. | The identification of specific interactions between HLA class I molecules and immunoregulatory MHC class I receptors, which provide an alternative approach to the understanding of how certain HLA class I alleles can impact on HIV-1 disease progression. | |
| 5. | The first description of the upregulation of specific inhibitory immunoregulatory molecules in individuals with spontaneous “elite” viral control, which might represent an active protective mechanism against immune over-activation in this specific patient population. | |
| Selected Publications of Interest: | ||
| 1. | Yu, XG*, Lichterfeld M*, Chetty S, Williams KL, Mui SK, Miura T, Frahm N, Feeney ME, Tang Y, Pereyra F, Labute MX, Pfafferott K, Leslie A, Crawford H, Allgaier R, Hildebrand W, Kaslow R, Brander C, Allen TM, Rosenberg ES, Kiepiela P, Vajpayee M, Goepfert PA, Altfeld M, Goulder PJ, Walker BD. Mutually exclusive T-cell receptor induction and differential susceptibility to human immunodeficiency virus type 1 mutational escape associated with a two-amino-acid difference between HLA class I subtypes. J Virol. 2007;81(4):1619-31. | |
| 2. | Lichterfeld M*, Kavanagh D*, Williams KL, Mosa B, Mui S, Miura T, Allgaier R, Pereyra F, Trocha A, Feeney M, Gandhi R, Rosenberg E, Altfeld M, Allen T, Allen R, Walker B, Sundberg E, Yu XG. A Viral CTL escape mutation leading to ILT4-mediated functional inhibition of myelomonocytic cells. J Exp Med. 2007; 204(12):2813-24. | |
| 3. | Lichterfeld M*, Mou D*, Cung HT, Williams KL, Waring MT, Huang J, Pereyra F, Trocha A, Freeman GJ, Rosenberg ES, Walker BD, Yu XG. Telomerase activity of HIV-1-specific CD8+ T cells: Constitutive upregulation in controllers and selective increase by blockade of PD ligand 1 in progressors. Blood, prepublished online August 26, 2008; DOI 10.1182/blood-2008-01-135442. | |
| 4. | Huang J, Goedert JJ, Sundberg EJ, Cung T, Burke P, Martin MP, Preiss L, Lifson J, Lichterfeld M, Carrington M, Yu XG. HLA-B*35-Px-mediated acceleration of HIV-1 infection by increased inhibitory immunoregulatory impulses. J Exp Med. 2009; 206(13):2959-2966. | |
| 5. | Huang J, Burke PS, Cung TD, Pereyra F, Toth I, Walker BD, Borges L, Lichterfeld M, Yu XG. Leukocyte immunoglobulin-like receptors maintain unique antigen-presenting properties of circulating myeloid dendritic cells in HIV-1-infected elite controllers. J Virol. 2010;84:9463-71. | |
| 6. | Chen H*, Li C*, Huang J*, Cung T*, Seiss K, Beamon J, Carrington MF, Porter LC, Burke PS, Yang Y, Ryan BJ, Liu R, Weiss RH, Pereyra F, Cress WD, Brass AL, Rosenberg ES, Walker BD, Yu XG, Lichterfeld M. CD4 T cells from elite controllers resist HIV-1 infection by selective upregulation of p21 (cip-1/waf-1). J. Clin. Invest. 2011. In press. | |
| Additional info: | ||
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Article on the Yu Lab in the Ragon Newsletter, October 2010 |
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