Immunological issues in vaccine trials: T-cell responses.

Abstract

T-cell responses are both extremely diverse and dependent on the MHC of the immunized (or infected) individual. Apart from T-cell proliferation assays, the most informative functional T-cell assays are still difficult to perform. Antibody measurements provide a very indirect assessment of the helper arm of the T-cell response. On the other hand, measuring cytolytic T cells (CTL) remains a difficult task, which has precluded the evaluation of CTL responses in vaccine efficacy trials. Accordingly, even though there are reasons to suspect that CTL are important to clear certain infections and to vaccinate against certain diseases, particularly chronic viral infections such as that caused infection by HIV, the data to support these claims are largely missing in humans. Improving and automating CTL assays would have a significant impact on vaccine design. The Immunoscope technology is a PCR based approach which describes the T cell repertoire by several thousands of measurements. This allows the detection of clonal expansions and to evaluate the oligoclonality of pathological T cell infiltrates in humans. In the mouse, it has allowed us to establish the concept of public T-cell responses which are recurrent in individual animals sharing the same MHC. This concept can occasionally apply to humans since we found a public T-cell expansion in DR2a patients at the onset of multiple sclerosis. Single chain class I MHC molecules have been produced, purified, homogeneously loaded with an antigenic peptide, and coated on to beads. This formulation appears to be efficient for induction of primary CTL in vitro . A similar approach can be used to purify peptide specific T cells, and its coupling with the Immunoscope technology is being considered. The potential of these new approaches for T-cell analyses will be discussed.