Immunodominant T-cell epitope on the F protein of respiratory syncytial virus recognized by human lymphocytes

Abstract

The lymphocyte proliferative responses to respiratory syncytial virus (RSV) were evaluated for 10 healthy adult donors and compared with proliferative responses to a chimeric glycoprotein (FG glycoprotein) which consists of the extracellular domains of both the F and G proteins of RSV and which is produced from a recombinant baculovirus. The lymphocytes of all 10 donors responded to RSV, and the proliferative responses to the whole virus were highly correlated with the responses to the FG glycoprotein. These data suggested that one or both of these glycoproteins of RSV were major target structures for stimulation of the human lymphocyte proliferative response among virus-specific memory T cells. The lymphocytes of four donors were evaluated further for their proliferative responses to a nested set of overlapping peptides modeled on the extracellular and cytoplasmic domains of the F protein of RSV. Strikingly, the lymphocytes of all 4 donors responded primarily to a region defined by a single peptide spanning residues 338 to 355, and the lymphocytes of 2 donors responded to an overlapping peptide spanning residues 328 to 342 also, thus defining a region of the F1 subunit within residues 328 to 355 that may circumscribe an immunodominant site for stimulation of human T cells from a variety of individuals. This region of the F protein is highly conserved among A and B subgroup viruses. As revealed by monoclonal antibody blocking studies, the lymphocytes responding to this antigenic site had characteristics consistent with T helper cells. Similar epitope mapping studies were performed with BALB/c mice immunized with the FG protein in which a relatively hydrophobic peptide spanning residues 51 to 65 within the F2 subunit appeared to be the major T cell recognition determinant. The data are discussed with respect to an antigenic map of the F protein and the potential construction of a synthetic vaccine for RSV.

Immunodominant T-cell epitopes of rubella virus structural proteins defined by synthetic peptides

“…Hybridoma cell lines (ATCC HB55 for L243, ATCC CRL8002 for OKT4, and ATCC CRL8014 for OKT8) were obtained from the American Type Culture Collection. Inhibition of antigenstimulated proliferation by MAbs was calculated as % inhibition = {1-[(cpm with peptide plus MAb)-(cpm with MAb)]/[(cpm with peptide)-(cpm with medium)]} x 100 (24). (41).…”

Epitope-specific airway-resident CD4+ T cell dynamics during experimental human RSV infection

“…Due to the low resting frequencies of RSV-specific CD4 + T cells, previous studies have focused on investigation of selected proteins by immortalization of T cell clones or in vitro expansion of PBMCs (29, 30, 46, 47). The limitations of these techniques rest in the inevitable bias introduced.…”

Genetic Vaccine for Respiratory Syncytial Virus Provides Protection Without Disease Potentiation

“…37 Another significant hurdle to overcome in development of a pediatric RSV vaccine is the legacy of vaccine-enhanced disease observed in the FI-RSV clinical trials. 7 While the precise molecular mechanism(s) underlying the generation of this immunopathologic immunity may not be fully elucidated, well-defined correlates of FI-RSV-enhanced RSV disease in children are induction of antibody responses with poor neutralization capacity 34 and enhanced eosinophil and/or neutrophil recruitment to the lung, 7,38 suggesting Th2-biased responses. 7,38,39 GC46.…”