Human CD8+ T cell responses against five newly identified respiratory syncytial virus-derived epitopes

Abstract

CD8+ T lymphocytes play a major role in the clearance of respiratory syncytial virus (RSV)infections. To be able to study the primary CTL response in RSV-infected children, epitopes presented by a set of commonly used HLA alleles (HLA-A1, -A3, -B44 and -B51) were searched for. Five epitopes were characterized derived from the matrix (M), non-structural (NS2) and second matrix (M2) proteins of RSV. All epitopes were shown to be processed and presented by RSV-infected antigen-presenting cells. HLA-A1 tetramers for one of these epitopes derived from the M protein were constructed and used to quantify and phenotype the memory CD8 + T cell pool in a panel of healthy adult donors. In about 60 % of the donors, CD8 + T cells specific for the M protein could be identified. These cells belonged to the memory T cell subset characterized by expression of CD27 and CD28, and down-regulation of CCR7 and CD45RA. The frequency of tetramer-positive cells varied between 0?4 and 3 per 10 4 CD8 + T cells in PBMC of healthy asymptomatic adult donors.

Serum Antibodies Critically Affect Virus-Specific CD4+/CD8+ T Cell Balance during Respiratory Syncytial Virus Infections

“…This finding illustrates the well-documented inhibitory effect of RSV infection on T cell proliferation (28,36,(43)(44)(45)(46). Using expanded virus-specific CD8 + T cell populations, we found similar IFN-g responses induced by HLA class I molecules on both virus-infected APCs and peptideloaded APCs.…”

“…In earlier work, we and others have shown that RSV-specific memory CD8 + T cells are present in adult PBMCs, although responses against single epitopes were low and, in most donors, not detectable without in vitro expansion (36)(37)(38)(39)(40)(41)(42). However, the virus-specific T cell response might be directed against a broad panel of HLA-presented peptides derived from the viral proteome (36,39).…”

“…However, the virus-specific T cell response might be directed against a broad panel of HLA-presented peptides derived from the viral proteome (36,39). In experiments presented in this study ( Fig.…”

“…Fig. 2B shows an example of in vitro T cell expansion poststimulation of PBMCs with peptide NS1 [41][42][43][44][45][46][47][48][49] derived from the nonstructural protein NS1, a peptide that is presented in the context of HLA-B51 (36). More than eight cell divisions were required to detect substantial numbers of IFN-g-producing CD8…”

CD8+ T Cell Responses in Bronchoalveolar Lavage Fluid and Peripheral Blood Mononuclear Cells of Infants with Severe Primary Respiratory Syncytial Virus Infections

“…With the introduction of HLA class I tetrameric complexes a method of direct detection of virus-specific cells was introduced. The recent characterization by our group (24) and others (23,(25)(26)(27) of several dominant RSV T cell epitopes provided the necessary tools to study the role of CD8 ϩ T cells during RSV infection. In the present study, we describe our investigation into the dynamics and function of the primary CD8 ϩ T cell response in the airways and peripheral blood during a localized severe primary respiratory infection.…”