Soluble HLA-A2.1 restricted peptides that are recognized by influenza virus specific cytotoxic T lymphocytes.
The influenza A virus matrix protein derived peptide with amino acids 57-68 (Lys-Gly-Ileu-Leu-Gly-Phe-Val-Phe-Thr-Leu-Thr-Val) is recognized by influenza virus HLA-A2 restricted CTL. Because of the large number of hydrophobic residues this peptide is very insoluble. Substitution with a number of polar amino acids resulted in a soluble peptide (Lys-Lys-Ala-Leu-Gly-Phe-Val-Phe-Thr-Leu-Asp-Lys) that was very effective in sensitizing HLA-A2 positive target cells. Further substitution of threonine in position 65 with lysine resulted in a soluble antagonist peptide that inhibited sensitization. Both agonist and antagonist peptides retained 20% of their biological activity when tyrosine was added at the N terminus. Soluble radio-iodinated peptides can now be prepared that will be useful reagents to study the interaction of peptides and class I molecules.
Bednarek
M A
MA
Merck Sharp and Dohme Research Laboratories, Rahway, NJ 07065.
Engl
S A
SA
Gammon
M C
MC
Lindquist
J A
JA
Porter
G
G
Williamson
A R
AR
Zweerink
H J
HJ
D000595:Amino Acid Sequence; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D012995:Solubility; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013912:Threonine; D014443:Tyrosine
D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D013912:Threonine; D014443:Tyrosine