Revelation of a cryptic major histocompatibility complex class II-restricted tumor epitope in a novel RNA-processing enzyme

CD4+ T-cell responses against human tumor antigens are a potentially critical component of the antitumor immune response. Molecular methods have been devised for rapidly identifying MHC class II-restricted tumor antigens and elucidating the recognized epitopes. We describe here the identification of...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2002-10, Vol.62 (19), p.5505-5509
Main Authors: TOPALIAN, Suzanne L, GONZALES, Monica I, WARD, Yvona, XIANG WANG, WANG, Rong-Fu
Format: Article
Language:English
Subjects:
Adult
Alleles
Amino Acid Sequence
Antigens, Neoplasm - immunology
Biological and medical sciences
CD4-Positive T-Lymphocytes - immunology
Epitopes, T-Lymphocyte - genetics
Epitopes, T-Lymphocyte - immunology
Gene Library
HLA-DR7 Antigen - immunology
Host-tumor relations. Immunology. Biological markers
Humans
Male
Medical sciences
Melanoma - enzymology
Melanoma - immunology
Molecular Sequence Data
Point Mutation
Polynucleotide Adenylyltransferase - genetics
Polynucleotide Adenylyltransferase - immunology
Polynucleotide Adenylyltransferase - metabolism
RNA, Neoplasm - metabolism
Subcellular Fractions - enzymology
Tumors
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Summary:CD4+ T-cell responses against human tumor antigens are a potentially critical component of the antitumor immune response. Molecular methods have been devised for rapidly identifying MHC class II-restricted tumor antigens and elucidating the recognized epitopes. We describe here the identification of neo-poly(A) polymerase (neo-PAP), a novel RNA processing enzyme overexpressed in a variety of human cancers, by screening a melanoma-derived invariant chain fusion cDNA library with tumor-reactive CD4+ T lymphocytes. A cryptic nonmutated HLA-DRbeta1*0701-restricted neo-PAP epitope was processed through the endogenous MHC class II pathway. A unique point mutation effected a nonconservative substitution of a leucine for a proline residue at a structurally important site in neo-PAP that was remote from the recognized peptide, revealing a normally silent epitope for immune recognition. Genetic aberrations such as the described point mutation can have unexpected immunological consequences, in this case leading to immune recognition of a distant normal self epitope.
ISSN:0008-5472
1538-7445