Immunogenicity of drug resistant HIV

Mason, Rosemarie (2005) Immunogenicity of drug resistant HIV. Masters thesis, Memorial University of Newfoundland.

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Abstract

Antiretroviral drug resistance and cytotoxic T lymphocyte (CTL) escape are considered to be major obstacles to effective control of human immunodeficiency virus (HIV). To investigate the possibility of combining drug and immune-based selective pressures to combat the emergence and transmission of HIV, we studied the effect of drug resistance mutations on CTL recognition of HIV -1 pol epitopes. Several drug resistance mutations sustained or even enhanced antigenicity and immunogenicity of HIV -1 epitopes. Thus, drug resistant HIV is susceptible to immune selective pressure which could be applied to combat transmission or emergence of drug resistance and enhance the immune response against HIV. We also observed instances of activation of CTL against a control self-peptide derived from interferon-gamma inducible protein (IP)-30 following in vitro stimulation with an HIV protease (PR) peptide. We found that activation of IP-30-specific CTL resulted from T cell cross-reactivity between the two peptides and indicates that HIV PR 76-84 peptide is a heteroclitic peptide variant (i.e. more immunogenic variant) of the IP-30 signal peptide, which may have implications for immune memory and autoimmunity.

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