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 proliferati on 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 don ors was mediated by CD4(+) T cells in association with HLA DR antigens . Over 70% of all donors tested responded to peptides representing ami no 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 infec ted and vaccinated donors were located in the genetically heterogeneou s carboxy-terminal half of the N, Analysis of patterns of peptide reac tivity among vaccinated and naturally infected subjects identified sev eral regions of potential difference between these two groups. Peptide s 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 v ersus transient immunity to measles. Use of chimeric molecules contain ing multiple well-characterized T- and B-cell epitopes or genetic alte ration of attenuated vaccine virus to enhance critical T-cell response s may eventually lead to the development of a vaccine candidate that c an more closely model the patterns of immune response elicited by wild -type virus. (C) 1997 Academic Press.