Peptide–MHC multimer-based monitoring of CD8 T-cells in HIV-1 infection and AIDS vaccine development

Abstract

The use of MHC multimers allows precise and direct detecting and analyzing of antigen-specific T-cell populations and provides new opportunities to characterize T-cell responses in humans and animals. MHC-multimers enable us to enumerate specific T-cells targeting to viral, tumor and vaccine antigens with exceptional sensitivity and specificity. In the field of HIV/SIV immunology, this technique provides valuable information about the frequencies of HIV- and SIV-specific CD8⁺ cytotoxic T lymphocytes (CTLs) in different tissues and sites of infection, AIDS progression, and pathogenesis. Peptide-MHC multimer technology remains a very sensitive tool in detecting virus-specific T -cells for evaluation of the immunogenicity of vaccines against HIV-1 in preclinical trials. Moreover, it helps to understand how immune responses are formed following vaccination in the dynamics from priming point until T-cell memory is matured. Here we review a diversity of peptide-MHC class I multimer applications for fundamental immunological studies in different aspects of HIV/SIV infection and vaccine development.

Keywords:

• affinity
• AIDS
• avidity
• CD4⁺ T-cells
• CD8⁺ CTL
• CD8⁺ T-cells
• cytokines
• HIV-1
• MHC class I molecules
• peptide-MHC multimer
• peptide-MHC tetramer
• SIV
• TCR
• vaccine

Acknowledgements

The authors thank Denis Antonets for help with Figure 1.

Financial & competing interests disclosure

The authors (AY Reguzova and LI Karpenko) were funded by the Russian Science Foundation grant 14-14-00660. This grant stimulated us to write this article. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Peptide-MHC multimers are essential research tools to detect rare populations of antigen specific CD8⁺ T-cells because of their high sensitivity, accuracy, and reproducibility.

• The pMHC multimer technique allows direct quantification of a single epitope-specific CD8⁺ T-cells, with the possibility of characterizing simultaneously their precise phenotypic and functional activity by recruiting additional methods.

• Peptide-MHC multimeric complexes bind with higher affinity to TCRs, which results in increased avidity and provides the opportunity to detect T-cells carrying TCRs with low affinity for MHC-peptide.

• The main limitation of the pMHC multimer is single epitope specificity for each pMHC complex.

• pMHC multimers are widely used to study the frequencies of antigen-specific CD8⁺ T-cells in different anatomical sites during acute and chronic HIV-1 infection and in the dynamics of disease progression and may help us to understand the pathogenesis of HIV-1 and HIV-1-associated diseases.

• Quantification of HIV-specific CD8⁺ T-cells in the course of infection along with studying systemic and mucosal immunity in AIDS patients and LNTPs may contribute to understanding of the immune correlates of protection.

• pMHC multimers are a valuable assay to estimate the efficacy of new vaccine candidates against HIV-1 in preclinical and clinical trials.