Effect of chain length on the conformation and T cell recognition of synthetic hemagglutinin fragments

Circular dichroism and Fourier-transform infrared spectroscopies were used to compare the conformational mobility of 13-mer peptides covering the 317- 329 region of the envelope protein hemagglutinin of human influenza A virus subtypes H1, H2 and H3 with that of their truncated deca- and nonapeptide analogs. These peptides were demonstrated to bind to the murine I-E-d major histocompatibility complex encoded class II and human HLA-B*2705 class I m olecules. Despite the amino acid substitutions in the three 13-mer subtype sequences, no significant differences in the conformational properties coul d be shown. Deletion of the N-terminal three residues resulted in a shift t o an increased alpha-helical conformer population in the 317-329 I-Il pepti de and the breakage of the 3(10) or weakly H-bonded (nascent) alpha-helix i n the H2 and H3 peptides. The conformational change observed upon deletion did not influence the efficiency of I-E-d-peptide interaction, however, the C-terminal Arg had a beneficial effect both on MHC class II and class I bi nding without causing any remarkable change in solution conformation. (C) 2 000 Elsevier Science B.V. All rights reserved.