Serum angiotensin-1 converting enzyme activity processes a human immunodeficiency virus 1 gp160 peptide for presentation by major histocompatibility complex class I molecules.
T cell stimulation by the human immunodeficiency virus 1 gp160-derived peptide p18 presented by H-2Dd class I major histocompatibility complex molecules in a cell-free system was found to require proteolytic cleavage. This extracellular processing was mediated by peptidases present in fetal calf serum. In vitro processing of p18 resulted in a distinct reverse phase high performance liquid chromatography profile, from which a biologically active product was isolated and sequenced. This peptide processing can be specifically blocked by the angiotensin-1 converting enzyme (ACE) inhibitor captopril, and can occur by exposing p18 to purified ACE. The ability of naturally occurring extracellular proteases to convert inactive peptides to T cell antigens has important implications for understanding cytotoxic T lymphocyte responses in vivo, and for rational peptide vaccine design.
Kozlowski
S
S
Molecular Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Corr
M
M
Takeshita
T
T
Boyd
L F
LF
Pendleton
C D
CD
Germain
R N
RN
Berzofsky
J A
JA
Margulies
D H
DH
D000595:Amino Acid Sequence; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002474:Cell-Free System; D015686:Gene Products, env / Q000276:immunology / Q000378:metabolism*; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007700:Kinetics; D007739:L Cells; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D011498:Protein Precursors / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D001613:beta 2-Microglobulin / Q000378:metabolism
D015686:Gene Products, env; D006183:H-2 Antigens; D019302:HIV Envelope Protein gp160; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D011498:Protein Precursors; D001613:beta 2-Microglobulin; D002216:Captopril; D002268:Carboxypeptidases; D007703:Peptidyl-Dipeptidase A