Shifting immunodominance pattern of two cytotoxic T-lymphocyte epitopes in the F glycoprotein of the Long strain of respiratory syncytial virus

• Published in: Journal of general virology 2004-11, Vol.85 (11), p.3229-3238
• Main Authors: Johnstone, Carolina, de Leon, Patricia, Medina, Francisco, Melero, Jose A, Garcia-Barreno, Blanca, Val, Margarita Del
• Format: Article
• Language: English
• Subjects: Amino Acid Motifs - immunology; Animals; Biological and medical sciences; CD8-Positive T-Lymphocytes - immunology; Cell Count; Cells, Cultured; Epitopes, T-Lymphocyte - genetics; Epitopes, T-Lymphocyte - immunology; Fundamental and applied biological sciences. Psychology; Human respiratory syncytial virus; Humans; Immunodominant Epitopes; Interferon-gamma - analysis; Ligands; Mice; Microbiology; Miscellaneous; Respiratory syncytial virus; Respiratory Syncytial Virus Vaccines - biosynthesis; Respiratory Syncytial Virus Vaccines - immunology; Respiratory Syncytial Virus, Human - immunology; Species Specificity; Spleen - immunology; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Cytotoxic - immunology; Vaccines, Synthetic - biosynthesis; Vaccines, Synthetic - immunology; Vaccinia virus; Vaccinia virus - genetics; Viral Proteins - immunology; Virology
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.80219-0

1 Unidade de Inmunología Viral, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra Pozuelo km 2, E-28220 Majadahonda (Madrid), Spain 2 Unidade de Biología Viral, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra Pozuelo km 2, E-28220 Majadahonda (Madrid), Spain Correspondence Margarita Del Val mdval{at}isciii.es Human respiratory syncytial virus (RSV) is a major cause of respiratory infection in children and in the elderly. The RSV fusion (F) glycoprotein has long been recognized as a vaccine candidate as it elicits cytotoxic T-lymphocyte (CTL) and antibody responses. Two murine H-2K d -restricted CTL epitopes (F85–93 and F92–106) are known in the F protein of the A2 strain of RSV. F-specific CTL lines using BCH4 fibroblasts that are persistently infected with the Long strain of human RSV as stimulators were generated, and it was found that in this strain only the F85–93 epitope is conserved. Motif based epitope prediction programs and an F2 chain deleted F protein encoded in a recombinant vaccinia virus enabled identification of a new epitope in the Long strain, F249–258, which is presented by K d as a 9-mer (TYMLTNSEL) or a 10-mer (TYMLTNSELL) peptide. The results suggest that the 10-mer might be a naturally processed endogenous K d ligand. The CD8 + T-lymphocyte responses to epitopes F85–93 and F249–258 present in the F protein of RSV Long were found to be strongly skewed to F85–93 in in vitro multispecific CTL lines and in vivo during a secondary response to a recombinant vaccinia virus that expresses the entire F protein. However, no hierarchy in CD8 + T-lymphocyte responses to F85–93 and F249–258 epitopes was observed in vivo during a primary response.