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Use of Interferon-γ Enzyme-linked Immunospot Assay to Characterize Novel T-cell Epitopes of Human Papillomavirus
Published on: March 8, 2012
Putative immunodominant human immunodeficiency virus-specific CD8(+) T-cell responses cannot be predicted by major
M R Betts1, J P Casazza, B A Patterson
1Department of Internal Medicine, Division of Infectious Diseases, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Insights
Focusing on a single epitope underestimates human immunodeficiency virus (HIV)-specific CD8(+) T-cell responses. Accurate measurement requires assessing all potential HIV epitopes, not just one, for a comprehensive understanding of immune activity.
Area of Science:
- Immunology
- Virology
- T-cell response
Background:
- Current research on human immunodeficiency virus (HIV)-specific CD8(+) T-cell responses often relies on single, typically HLA-A2-restricted epitopes.
- The assumption that a response to one epitope reflects the overall immune response to HIV remains unverified.
Purpose of the Study:
- To investigate epitope immunodominance and the complexity of HIV-specific CD8(+) T-cell responses.
- To determine if responses to a single epitope accurately represent the total CD8(+) T-cell response to HIV.
Main Methods:
- Utilized cytokine flow cytometry to analyze CD8(+) T-cell responses in 11 HIV-positive individuals with HLA-A2.
- Assessed responses to the HLA-A2-restricted p17 epitope (SLYNTVATL) and other HIV peptides restricted by various HLA class I alleles.
Main Results:
- Only 4 out of 11 patients recognized the p17 epitope SLYNTVATL.
- Most non-responders to the p17 epitope recognized other HIV epitopes.
- Some responders to p17 had stronger responses to epitopes restricted by different HLA alleles.
- In some cases, CD8(+) T-cell responses were detected against non-HLA-A2-restricted epitopes, even when no HLA-A2 response was observed.
Conclusions:
- An individual's overall CD8(+) T-cell response to HIV is not accurately represented by responses to a single epitope.
- Major histocompatibility complex class I alleles do not reliably predict immunodominant responses restricted by that allele.
- Comprehensive quantification of total HIV-specific CD8(+) T-cell responses necessitates evaluating all potential epitopes.
Abstract:
Recent studies of human immunodeficiency virus (HIV)-specific CD8(+) T cells have focused on responses to single, usually HLA-A2-restricted epitopes as surrogate measures of the overall response to HIV. However, the assumption that a response to one epitope is representative of the total response is unconfirmed. Here we assess epitope immunodominance and HIV-specific CD8(+) T-cell response complexity using cytokine flow cytometry to examine CD8(+) T-cell responses in 11 HLA-A2(+) HIV(+) individuals. Initial studies demonstrated that only 4 of 11 patients recognized the putative immunodominant HLA-A2-restricted p17 epitope SLYNTVATL, suggesting that the remaining subjects might lack significant HIV-specific CD8(+) T-cell responses. However, five of six SLYNTVATL nonresponders recognized other HIV epitopes, and two of four SLYNTVATL responders had greater responses to HIV peptides restricted by other class I alleles. In several individuals, no HLA-A2-restricted epitopes were recognized, but CD8(+) T-cell responses were detected to epitopes restricted by other HLA class I alleles. These data indicate that an individual's overall CD8(+) T-cell response to HIV is not adequately represented by the response to a single epitope and that individual major histocompatibility complex class I alleles do not predict an immunodominant response restricted by that allele. Accurate quantification of total HIV-specific CD8(+) T-cell responses will require assessment of the response to all possible epitopes.
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