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The Altfeld laboratory studies innate immune responses in HIV-1 infection, and their consequences of adaptive immunity to HIV-1. The laboratory has three major areas of interest: a) The analysis of HIV-1-specific CD8+ T cell responses in Acute HIV-1 Infection, with particular focus on the mechanisms that determine the functionality and immunodominance of HIV-1-specific CD8+ T cell responses during the initial phase of HIV-1 infection. b) The analysis of Innate Immune Responses in HIV-1 infection, specifically focusing on the role of NK cells in HIV-1 infection and the impact of Toll-like Receptor (TLR) ligands on modulating the function of immune cells. c) The monitoring of HIV-1-specific immune response in individuals undergoing prophylactic or therapeutic immunizations to understand the immune correlates of HIV-1 control.
Furthermore, Dr. Altfeld is interested in characterizing immune responses directed against HIV-1 in populations of different ethnicities affected by the epidemic, and has close collaboration with the HIV-1 Pathogenesis Program at the Nelson Mandela School of Medicine at the University of KwaZulu-Natal in Durban, South Africa, and the Department of Infectious Diseases at the Tangdu Hospital in Xi’an, China.
| Present Areas of Investigation: |
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Characterization of the mechanisms responsible for the immunodominance pattern of HIV-1-specific T cell responses during Acute HIV-1 Infection. |
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Assessment of the changes in HIV-1-specific CD8+ T cell function during primary HIV-1 infection and the impact of therapeutic immunization on HIV-1-specific CD8+ T cell function. |
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Characterization of the role of Natural Killer cells in the control of HIV-1 infection. |
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Characterization of the impact of Toll-like receptor ligation on the function of innate and adaptive immunity. |
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| Important Accomplishments: |
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Detailed characterization of the immunodominance pattern of HIV-1-specific CD8+ T cell responses in Acute HIV-1 Infection. |
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Demonstration that HIV-1-specific CD8+ T cell proliferation in vitro depends on the support of CD4+ T helper cells. |
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First description of superinfection with an HIV-1 clade B strain in an HIV-1 clade B infected subject. |
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Demonstration that specific Natural Killer cell populations can mediate strong antiviral activity against HIV-1. |
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Identification of several TLR7/8 ligands within the ssRNA of HIV-1, and their role in modulating HIV-1 immunity. |
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| Selected Publications of
Interest: |
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Altfeld M, Allen TM, Yu XG, Johnston MN, Agrawal D, Korber BT, Montefiori DC, O'Connor DH, Davis BT, Lee PK, Maier E, Harlow J, Goulder PJR, Brander C, Rosenberg ES, Walker BD. HIV-1 superinfection despite broadly directed CD8+ T cell responses containing replication of the primary virus. Nature 2002, 420:434-439 |
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Lichterfeld M, Kaufmann DE, Yu XG, Mui SK, Addo MM, Johnston MN, Cohen D, Robbins GK, Pae E, Alter G, Wurcel A, Stone D, Rosenberg ES, Walker BD, Altfeld M. Loss of HIV-1-specific CD8+ T cell proliferation after acute HIV-1 infection and restoration by vaccine-induced HIV-1-specific CD4+ T cells. J Exp Med. 2004. 20;200(6):701-12 |
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Alter G, Martin MP, Teigen N, Carr WH, Suscovich TJ, Schneidewind A, Streeck H, Waring M, Meier A, Brander C, Lifson JD, Allen TM, Carrington M, Altfeld M. Differential natural killer cell-mediated inhibition of HIV-1 replication based on distinct KIR/HLA subtypes. J Exp Med. 2007 Nov 26;204(12):3027-36 |
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Streeck H, Brumme ZL, Anastario M, Cohen KW, Jolin JS, Meier A, Brumme CJ, Rosenberg ES, Alter G, Allen TM, Walker BD, Altfeld M. Antigen load and viral sequence diversification determine the functional profile of HIV-1-specific CD8+ T cells. PLoS Med. 2008 May 6;5(5):e100. |
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Meier A, Chang JJ, Chan ES, Pollard RB, Sidhu HK, Kulkarni S, Wen TF, Lindsay RJ, Orellana L, Mildvan D, Bazner S, Streeck H, Alter G, Lifson JD, Carrington M, Bosch RJ, Robbins GK, Altfeld M. Sex differences in the Toll-like receptor-mediated response of plasmacytoid dendritic cells to HIV-1. Nat Med. 2009 Aug;15(8):955-9. |
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