Cytotoxic T cells isolated from ovarian malignant ascites recognize a peptide derived from the HER-2/neu proto-oncogene.
The HER-2/neu proto-oncogene encodes a transmembrane receptor protein whose expression is enhanced in a number of breast and ovarian tumors and correlates with tumor aggressiveness, suggesting that it may play an important role in tumor growth. Recent evidence suggests that HER-2/neu may be a potential candidate for targeted immune intervention. In this report we show that cytotoxic T lymphocytes (CTL) expanded from tumor-associated lymphocytes with HLA-A2+ and HER-2/neu+ tumors can specifically recognize synthetic peptides corresponding to amino acids 971-980 of HER-2/neu protein. This sequence includes a potential amphiphilic area containing both Rothbard's epitode motifs and HLA-A2 anchor residues. Our study provides the first direct evidence of HER-2/neu-reactive CTL in humans. The fact that these HER-2/neu peptide-reactive CTL show significantly lower reactivity with corresponding EGF-R peptides offers new perspectives for understanding the recognition of self-antigens by tumor-reactive T cells.
Ioannides
C G
CG
Department of Gynecologic Oncology, M. D. Anderson Cancer Center, Houston, Texas 77030.
Fisk
B
B
Fan
D
D
Biddison
W E
WE
Wharton
J T
JT
O'Brian
C A
CA
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000276:immunology*; D001201:Ascites / Q000276:immunology; D002460:Cell Line; D000939:Epitopes / Q000276:immunology; D066246:ErbB Receptors / Q000276:immunology*; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000276:immunology*; D018719:Erb-b2 Receptor Tyrosine Kinases; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D000939:Epitopes; D066246:ErbB Receptors; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human