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Mapping of the genes encoding tum- transplantation antigens P91A, P35B, and P198
P J Dyson1, C de Smet, A M Knight
1Clinical Research Centre, Harrow, Middlesex, UK.
Abstract:
Tum- comprises a class of genes, mutation of which in P815 tumor cells has led to the acquisition of new cytotoxic T cell-recognized epitopes. The cells carrying the mutant alleles have impaired tumorigenicity compared with their progenitors due to in vivo induction of a cytotoxic T-cell response specific for tum- antigens. Two tum- genes, P91A and P35B, were found to be single copy loci mapping to chromosomes 11 and 15 respectively. A third, P198, was found to map to chromosome 7 and to be a member of a small gene family with other members on chromosomes 13, 14, and 15. Multiple P198-related sequences were found in other mammalian species suggesting the P198 related gene family is a general feature of mammalian genomes.
Insights
Mutations in tumor (Tum-) genes create new antigens recognized by cytotoxic T cells, reducing tumor cell growth. This study maps key Tum- genes and reveals a conserved gene family across mammals.
Area of Science:
- Immunology
- Genetics
- Oncology
Background:
- Tumor (Tum-) genes encode antigens recognized by cytotoxic T cells.
- Mutations in Tum- genes can lead to the development of novel T cell epitopes.
- Tumor cells with mutant alleles exhibit reduced tumorigenicity due to T cell responses.
Purpose of the Study:
- To identify and characterize the chromosomal localization of specific Tum- genes.
- To investigate the genetic basis of impaired tumorigenicity in cells with mutant Tum- alleles.
- To explore the evolutionary conservation of Tum- gene families in mammals.
Main Methods:
- Analysis of P815 tumor cells with mutations in Tum- genes.
- Chromosomal mapping of identified Tum- genes (P91A, P35B, P198).
- Comparative sequence analysis to identify related gene families in other mammalian species.
Main Results:
- Two Tum- genes, P91A and P35B, were mapped to chromosomes 11 and 15, respectively.
- A third Tum- gene, P198, was mapped to chromosome 7 and identified as part of a gene family.
- P198-related sequences were found in multiple mammalian species, indicating evolutionary conservation.
Conclusions:
- Mutant Tum- antigens induce specific cytotoxic T cell responses, impairing tumor growth.
- The chromosomal locations of P91A, P35B, and P198 have been determined.
- The P198-related gene family is a conserved feature in mammalian genomes, suggesting functional importance.