The attachment (G) glycoprotein of respiratory syncytial virus contains a single immunodominant epitope that elicits both Th1 and Th2 CD4+ T cell responses.
BALB/c mice immunized with a vaccinia virus expressing the attachment (G) glycoprotein of respiratory syncytial virus (RSV) develop a virus-specific CD4(+) T cell response that consists of a mixture of Th1 and Th2 CD4(+) T cells following intranasal infection with live RSV. Recent work has shown that both Th1 and Th2 CD4(+) T cells are elicited to a single region comprising aa 183-197 of the G protein. To more precisely define the CD4(+) T cell epitope(s) contained within this region, we created a panel of amino- and carboxyl-terminal truncated as well as single alanine-substituted peptides spanning aa 183-197. These peptides were used to examine the ex vivo cytokine response of memory effector CD4(+) T cells infiltrating the lungs of G-primed RSV-infected mice. Analysis of lung-derived memory effector CD4(+) T cells using intracellular cytokine staining and/or ELISA of effector T cell culture supernatants revealed a single I-E(d)-restricted CD4(+) T cell epitope with a core sequence mapping to aa 185-193. In addition, we examined the T cell repertoire of the RSV G peptide-specific CD4(+) T cells and show that the CD4(+) T cells directed to this single immunodominant G epitope use a restricted range of TCR Vss genes and predominantly express Vss14 TCR.
Varga
S M
SM
Beirne B. Carter Center for Immunology Research and Departments of Microbiology and Pathology, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.
Wissinger
E L
EL
Braciale
T J
TJ
D000409:Alanine / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015707:HN Protein; D016056:Immunodominant Epitopes / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D007156:Immunologic Memory; D016130:Immunophenotyping; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D015707:HN Protein; D016056:Immunodominant Epitopes; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C116204:attachment protein G; D000409:Alanine