Use of synthetic peptides to identify measles nucleoprotein T-cell epitopes in vaccinated and naturally infected humans.

Recombinant measles nucleoprotein (N) and synthetic peptides spanning the length of the N-protein-coding region were used with a proliferation assay to identify human T-cell epitopes in vaccinated and naturally infected adults. A number of epitopes were mapped to specific regions of the measles virus N. The proliferative response of at least two donors was mediated by CD4(+) T cells in association with HLA DR antigens. Over 70% of all donors tested responded to peptides representing amino acids 271-290, 367-386, 400-420, and 483-502, suggesting that these peptides may be broadly recognized within an HLA diverse population. The most frequently recognized T-cell epitopes in both naturally infected and vaccinated donors were located in the genetically heterogeneous carboxy-terminal half of the N. Analysis of patterns of peptide reactivity among vaccinated and naturally infected subjects identified several regions of potential difference between these two groups. Peptides 221-240 and 237-256 were recognized among 100% of naturally infected donors but among only 37.5% of vaccinated donors and therefore may be of further interest in studies to investigate induction of lifelong versus transient immunity to measles. Use of chimeric molecules containing multiple well-characterized T- and B-cell epitopes or genetic alteration of attenuated vaccine virus to enhance critical T-cell responses may eventually lead to the development of a vaccine candidate that can more closely model the patterns of immune response elicited by wild-type virus.