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Identification and quantification of a naturally presented peptide as recognized by cytotoxic T lymphocytes specific
1Max-Planck-Institut für Biologie, Abteilung Immungenetik, Tübingen, Germany.
Abstract:
The target antigen recognized by H-2Kd-restricted cytotoxic T lymphocytes (CTLs) specific for a mutagen-induced antigen on DBA/2-derived tumor P815 was identified as the product of a normal cellular gene encompassing a point mutation. Using synthetic peptides, the epitope recognized by these CTLs was narrowed down to be contained within the undecamer KYQAVTTTLEE, incorporating the point mutation. The allele-specific peptide motif for H-2Kd molecules allowed us to predict the peptide naturally presented by the tumor cells to be the nonamer KYQAVTTTL. Isolation of the natural tum(-)-specific peptide from P198.3 tumor cells and biochemical comparison with the synthetic nonamer confirmed the prediction. This natural nonapeptide is represented by approximately 100 copies per tumor cell.
Insights
Researchers identified a mutated cellular gene product as the target antigen for cytotoxic T lymphocytes (CTLs) in a specific tumor. The study pinpointed the exact mutated peptide epitope responsible for the anti-tumor immune response.
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- Cytotoxic T lymphocytes (CTLs) play a crucial role in anti-tumor immunity.
- Identifying tumor-specific antigens is vital for developing targeted cancer therapies.
- Mutations in cellular genes can lead to the generation of neoantigens recognized by CTLs.
Purpose of the Study:
- To identify the specific antigen recognized by H-2Kd-restricted CTLs against a mutagen-induced tumor.
- To determine the precise epitope of the identified antigen.
- To validate the naturally processed peptide presented by tumor cells.
Main Methods:
- Utilized CTLs specific for a mutagen-induced antigen on DBA/2-derived tumor P815.
- Employed synthetic peptides to map the epitope.
- Predicted the naturally presented peptide using H-2Kd allele-specific peptide motifs.
- Isolated and biochemically compared the natural peptide from tumor cells.
Main Results:
- The target antigen was identified as a product of a normal cellular gene with a point mutation.
- The CTL epitope was localized to an undecamer peptide containing the mutation.
- The naturally presented nonamer peptide KYQAVTTTL was predicted and confirmed.
- Approximately 100 copies of this nonapeptide are present per tumor cell.
Conclusions:
- The study successfully identified a mutated self-peptide acting as a tumor-specific antigen.
- This finding elucidates the molecular basis of CTL recognition of a mutagen-induced tumor antigen.
- The identified peptide and its presentation mechanism provide insights for potential immunotherapeutic strategies.