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Effective HIV control may depend on viral protein targeted by immune cells

An effective response of the immune system’s ‘killer?T cells against infection with HIV may depend on exactly which viral protein is targeted, according to an international group of researchers. A new study finds that HIV-infected individuals in whom virus-specific CD8 T cells are targeted against the Gag protein have lower viral levels than do those with CD8 responses directed against other viral proteins. The report from the Partners AIDS Research Center at Massachusetts General Hospital (PARC-MGH), the University of Oxford and University of KwaZulu-Natal in South Africa is receiving early online release in Nature Medicine.

"Understanding which immune responses are effective in control of HIV is of critical importance in vaccine development," says Philip Goulder, MD, PhD, of PARC-MGH and Oxford, the senior author of the study. "Previous approaches have focused on a ‘more is better?approach, seeking to generate responses against a broad range of viral proteins, but these results challenge that dogma."

While many strategies for developing a vaccine to control HIV focus on the activity of the CD8 T lymphocytes that recognize and destroy virus-infected CD4 T cells, the fact that even patients in the last stages of AIDS can have measurable CD8 responses indicates that those responses are not always effective. To investigate how variations in CD8 response alter the ability to control HIV, the research team enrolled almost 600 South African patients who had not yet been treated for their HIV infections.

The researchers comprehensively mapped the CD8 responses against all viral proteins and also investigated whether the versions of HLA Class I molecules involved in the immune system’s recognition of HIV protein fragments made a difference. When new viruses are produced within an infected cell, Class I molecules grab viral fragments and display them at the cell surface, thereby alerting CD8 cells that the cell has been infected and shoul
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Source:Massachusetts General Hospital


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