Antibodies specific for the
hemagglutinin (HA)
protein of influenza virus are critical for protective immunity to
infection. Our studies show that CD4 T cells specific for
epitopes derived from HA are the most effective in providing help for the HA-specific B cell responses to
infection and vaccination. In this study, we asked whether HA
epitopes recognized by CD4 T cells in the primary response to
infection are equally distributed across the HA
protein or if certain segments are enriched in CD4
T cell epitopes. Mice that collectively expressed eight alternative MHC (Major Histocompatibility Complex) class II molecules, that would each have different
peptide binding specificities, were infected with an H1N1 influenza virus. CD4 T cell
peptide epitope specificities were identified by
cytokine EliSpots. These studies revealed that the HA-specific CD4
T cell epitopes cluster in two distinct regions of HA and that some segments of HA are completely devoid of CD4
T cell epitopes. When located on the HA structure, it appears that the regions that most poorly recruit CD4 T cells are sequestered within the interior of the HA trimer, perhaps inaccessible to the proteolytic machinery inside the endosomal compartments of antigen presenting cells.