The HLA-DP peptide repertoire from human respiratory syncytial virus is focused on major structural proteins with the exception of the viral polymerase.

The recognition by specific T helper cells of viral antigenic peptides complexed with HLA class II molecules exposed on the surface of antigen presenting cells is the first step of the complex cascade of immunological events that generates the protective cellular and humoral immune responses. The HLA class II-restricted helper immune response is critical in the control and the clearance of human respiratory syncytial virus (HRSV) infection, a pathogen with severe health risk in pediatric, immunocompromised and elderly populations. In this study, a mass spectrometry analysis was used to identify HRSV ligands bound to HLA-DP class II molecules present on the surface of HRSV-infected cells. Among the thousands of cellular peptides bound to HLA class II proteins in the virus-infected cells, sixty-four naturally processed viral ligands, most of them included in complex nested set of peptides, were identified bound to HLA-DP molecules. These viral ligands arose from five of six major structural HRSV proteins: attachment, fusion, matrix, nucleoprotein, and phosphoprotein. In contrast, no HLA-DP ligands were identified from polymerase protein, the largest HRSV protein that includes half of the viral proteome. These findings have important implications for analysis of the helper immune response as for antiviral vaccine design. SIGNIFICANCE: The existence of a supertype including five alleles that bind a peptide repertoire very similar make HLA-DP class II molecules an interesting target for the design of vaccines. Here, we analyze the HLA-DP-restricted peptide repertoire against the human respiratory syncytial virus, a pathogen that represents a high health risk in infected pediatric, immunocompromised and elderly populations. This repertoire is focused on major structural proteins with the exception of the viral polymerase.