The feline major histocompatibility complex (MHC) has been studied using molecular techniques as an approach to comparative genome organization of this important gene cluster. The MHC encodes two types of cell surface antigens (class I and class II) and controls immune responses by presenting immunological peptides to T-cell receptors. Feline MHC genes are located near the centromere of chromosome B2. Both class I and class II antigens of feline MHC have polymorphic features like other mammalian MHC. Sequence analysis of MHC class I molecules from three feline species--domestic cat, cheetah, and ocelot--which represent three major feline groups, revealed that feline MHC class I molecules have highly mosaic structures in their entire coding regions. We identify at least 15 mosaic regions where each has at least two polymorphic sequence motifs. A majority of such motifs was found in at least two species. Moreover, very similar sequence motifs were identified in polymerase chain reaction (PCR)-amplified sequences from 14,000-year-old asphalt-preserved fossil bones of the extinct saber-tooth cat. Some of these sequence motifs are conserved not only in Felidae MHC class I sequences but also in some human, orangutan, and bovine MHC class I sequences. These data revealed that modern polymorphic sequence motifs found in mammalian MHC class I molecules are extremely ancient, and shuffling of these motifs by DNA recombination plays a pivotal role in producing novel polymorphic MHC class molecules in mammals.
