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247 Structural Similarities between Influenza Virus and HIV Matrix Proteins Results in Cross-Recognition by T Cells from Both HIV-Infected and Uninfected Individuals
P. M. Acierno, D. A. Newton, E. A. Brown, L. Maes, J. E. Baatz, and S. Gattoni-Celli*
Med. Univ. of South Carolina, Charleston, USA
Background: It has been reported that the matrix protein of the influenza A virus and the matrix and capsid proteins of the human immunodeficiency virus (HIV) share striking structural similarities as determined by x-ray crystallography. This coincidence led us to investigate the existence of possible cross-reactivity between FLU-M158-66 (FLU) and HIV-1 p17 GAG77-85 (GAG) epitopes following in vitro stimulation of peripheral blood mononuclear cells (PBMC) derived from either HIV-infected or uninfected HLA-A2+ donors.
Methods: Cross-reactivity of the peptide epitopes was investigated by use of cytotoxicity studies, HLA tetramer analyses, cytokine-release assays, and clonotype mapping of the beta-chain gene of the T-cell receptor (TCR-b).
Results: In vitro stimulation of PBMC from an HLA-A2+, HIV-seropositive donor with either FLU or GAG peptide induced cytotoxic T lymphocytes (CTL) capable of HLA-restricted killing of target cells loaded with either FLU or GAG peptide. Parallel experiments demonstrated that CD3+/CD8+ lymphocytes stimulated with either FLU or GAG peptide were able to recognize both FLU and GAG HLA-A2 tetramers. For PBMC from an HLA-A2+, HIV-seronegative donor, in vitro stimulation with FLU peptide was capable of generating a cytotoxic response against target cells loaded with either FLU or, to a lesser extent, GAG peptide. This result was collaborated by interferon (IFN)-gamma-release assays. Furthermore, following stimulation with either FLU or GAG peptide, CD3+/CD8+ lymphocytes from this donor were able to recognize FLU HLA-A2 tetramers. Analysis of TCR-beta cDNA in lymphocytes from the seronegative donor strongly suggests that cross-recognition of FLU and GAG epitopes results from in vitro expansion of some identical T-cell clonotypes.
Conclusions: These experimental results suggest that immunity to structural components of the influenza virus may drive a specific immune response to structural components of HIV in both infected and uninfected individuals. Taken together, these observations may have practical implications not only for immunotherapy of HIV-infected patients, but also for prevention of HIV infection.
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