tab001smc: Currently available in vitro methods for stimulating T cells that are specific for human papillomaviruses (HPVs) (tab001smc)

Stephen Man

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Table 1. Currently available in vitro methods for stimulating T cells that are specific for human papillomaviruses (HPVs) (tab001smc)

Method 1
Stimulus/source of HPV antigen: HPV-transformed tumour cell.
Phenotype of responding cells: Mostly CD8⁺ T cells.
Advantages: T cells that can recognise naturally processed tumour antigens are generated. If tumour cells and PBMCs are from the same donor, it is possible to obtain T cells recognising tumour antigens that are unique to that individual. It is possible to generate tumour-specific CTLs, reactive against non-HPV antigens.
Disadvantages: It is difficult to grow keratinocytes in vitro, and tumour cells change their properties in culture. If a non-autologous tumour line is used, an allogeneic response might occur.

Method 2
Stimulus/source of HPV antigen: Cells transfected with HPV DNA, by DNA transfection or use of recombinant viral vectors (such as vaccinia and adenovirus).
Phenotype of responding cells: Mostly CD8⁺ T cells.
Advantages: Can identify T cells that are specific for individual HPV-gene products. Can infect HLA-typed cells, for example with the same HLA type as the donor.
Disadvantages: The peptides processed from these HPV antigens might not be the same as those found on HPV-transformed tumour cells.

Method 3
Stimulus/source of HPV antigen: Recombinant, soluble HPV proteins.
Phenotype of responding cells: Mostly CD4⁺ T cells.
Advantages: Can detect responses to individual HPV-gene products. Can infect HPV-typed cells, for example with the same HLA type as the donor.
Disadvantages: It is difficult to control for specificity. Proteins can be impure or contaminated with proteins from the vector/purification method. The peptides processed from these HPV antigens might not be the same as those found on HPV-transformed tumour cells.

Method 4
Stimulus/source of HPV antigen: Synthetic peptides derived from HPV protein sequences.
Phenotype of responding cells: CD8⁺ or CD4⁺ T cells.
Advantages: Can detect T-cell responses to individual HPV-gene products. Can detect T-cell responses to single peptide–MHC combinations. Can map T-cell epitopes within a known protein sequence for sub-unit vaccine design.
Disadvantages: To study T-cell responses against a single HPV-gene product, a large number of peptides needs to be made; this can be prohibitively expensive if the protein is large. If the number of peptides that are to be synthesised is reduced by using predictive ‘motifs’, epitopes might be missed. Peptides that are immunogenic to T cells in vitro might not be the same as the peptides processed and presented on HPV-transformed tumour cells.

Abbreviations: CTLs = cytotoxic T lymphocytes, a type of T cell that typically has the CD8 cell-surface receptor (CD8⁺); CD4 = a cell-surface receptor that is typically found on T-helper lymphocytes; PBMCs = peripheral blood mononuclear cells, including T cells and some circulating antigen-presenting cells; HLA = human leucocyte antigen, the human form of major histocompatibility complex (MHC) antigen.

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