Despite strong virus-specific humoral and cellular immune responses, disease progression ensues in the vast majority of HIV infected individuals indicating that the host immune response is typically unable to control infection. Understanding the failure of these immune responses is a central component in understanding HIV pathogenesis and developing strategies for effective vaccines and immune based therapies. Virus-specific T helper cells are critical for the maintenance of effective immunity in most chronic viral infections, however in the majority of HIV infected individuals, these cells are weak or absent in all stages of disease and represent a major defect in the immune response against this virus. HIV-specific T helper cells perform an essential role in the control of HIV replication through the collaboration with cytotoxic T lymphocytes, neutralizing antibody and possibly via direct antiviral effects. However our understanding of these critical immune responses is far from complete and the reason why some infected individuals control HIV replication while others do not is unclear. The goal of this proposal is to perform an in-depth characterization of HIV-specific T helper cell responses in an attempt to further our understanding of the relationship between HIV-specific T helper cells and the pathogenesis of infection. Specifically, we propose: 1. To determine the evolution of HIV-specific T helper cell responses in terms of the magnitude, breadth, specificity and functionality in persons who maintain control of viremia and in persons who lose control of viremia. 2. To determine the precise epitopes targeted by HIV-specific T helper cells as well as the restricting class II alleles, using unique cohorts of persons with acute/early HIV infection and in persons with long-term spontaneous control of viremia. 3. To determine whether sequence variation within HIV T helper cell epitopes leads to functional immune escape.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI040873-05A2
Application #
6553769
Study Section
AIDS and Related Research 8 (AARR)
Program Officer
Plaeger, Susan F
Project Start
1997-09-30
Project End
2007-04-30
Budget Start
2002-05-15
Budget End
2003-04-30
Support Year
5
Fiscal Year
2002
Total Cost
$354,108
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
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