Immunogenicity of free synthetic peptides corresponding to T helper epitopes of the influenza HA 1 subunit. Induction of virus cross reacting CD4+ T lymphocytes in mice

Abstract

Four linear synthetic peptides corresponding to residues 12-29, 50-67, 121-138 and 131-147 of the HA 1 subunit of H3 subtype influenza virus (NT/60/68) were tested for their capacity to elicit in vivo peptide-specific CD4+ T cells cross reacting with whole virus. By studying the in vitro peptide proliferative response of lymph node cells from mice sensitized in vivo with free peptides emulsified in complete or incomplete Freund adjuvant, it was found that region 12-29 could be recognized by CD4+ T lymphocytes in the context of H-2k and H-2b, region 50-67 in association with H-2b and region 121-138 in the context of H-2d MHC molecules. Outbred OF 1 mice could recognize regions 50-67 and 121-138. Peptides 50-67 and 121-138 are of potential interest for synthetic vaccine design since they induced in BALB/c (peptide 121-138) and OF 1 (both peptides) mice a CD4+ T cell population that cross reacted with whole virus. The region 50-67 is of particular interest since only few substitutions have been found in this area in natural variants of the H3 virus subtype.