Cloning and characterization of a polymorphic class I MHC gene in the AKR lymphoma K36.16

Cancers are the result of somatic heritable changes in certain genes. The AKR leukaemia K36.16 has been extensively studied in our laboratory. When compared to normal AKR thymocytes, the K36.16 tumour cells do not express the H-2Kk antigens and have an unexpected antigenic determinant that could be detected by anti-H-2Dd monoclonal antibodies. To understand the molecular mechanisms that could be responsible for these changes, we have compared the genomic composition of the class I MHC genes in the K36.16 tumour cells to that of normal AKR lymphocytes. A unique polymorphic 2.6-kb Hind III fragment was detected in DNA obtained from the K36.16 tumour cells after hybridization with a 3'-gene-coding H-2 probe. This fragment is not present in DNA of normal AKR lymphocytes. In an effort to further understand the mechanism underlying the nature of this MHC gene polymorphism, we have cloned and sequenced this Hind III fragment. When compared with the reported sequences of a number of mouse class I MHC genes, the nucleotide sequence of this polymorphic Hind III fragment is similar to that of a reported Tla gene.