A peptide recognized by human cytolytic T lymphocytes on HLA-A2 melanomas is encoded by an intron sequence of the N-acetylglucosaminyltransferase V gene.
A cytolytic T lymphocyte (CTL) clone that lyses many HLA-A2 melanomas was derived from a population of tumor-infiltrating lymphocytes of an HLA-A2 melanoma patient. The gene coding for the antigen recognized by this CTL was identified by transfection of a cDNA library. It is the gene which has been reported to code for N-acetylglucosaminyltransferase V (GnT-V). Remarkably, the antigenic peptide recognized by the CTL is encoded by a sequence located in an intron. In contrast to the fully spliced GnT-V mRNA, which was found in a wide range of normal and tumoral tissues, the mRNA containing the intron region coding for the antigen was not found at a significant level in normal tissues. This mRNA was observed to be present in about 50% of melanomas. Our results suggest that a promoter located near the end of the relevant intron is activated in melanoma cells, resulting in the production of an mRNA coding for the antigen.
Guilloux
Y
Y
Ludwig Institute for Cancer Research, Brussels Branch and Cellular Genetics Unit, Université Catholique de Louvain, Belgium.
Lucas
S
S
Brichard
V G
VG
Van Pel
A
A
Viret
C
C
De Plaen
E
E
Brasseur
F
F
Lethé
B
B
Jotereau
F
F
Boon
T
T
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics*; D001483:Base Sequence; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D017931:DNA Primers; D018076:DNA, Complementary; D005260:Female; D015870:Gene Expression; D015723:Gene Library; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D007438:Introns; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008545:Melanoma / Q000201:enzymology / Q000235:genetics* / Q000276:immunology*; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D019105:Random Amplified Polymorphic DNA Technique; D015183:Restriction Mapping; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D017931:DNA Primers; D018076:DNA, Complementary; D015789:HLA-A2 Antigen; D012333:RNA, Messenger; D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase