The Attachment (G) Glycoprotein of Respiratory Syncytial Virus Contains a Single Immunodominant Epitope That Elicits Both Th1 and Th2 CD4+ T Cell Responses

Abstract

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-Ed-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 Vβ genes and predominantly express Vβ14 TCR.