Analysis of the nucleotide sequence variation of the antigen-binding domain of DRα and DQα molecules as related to the evolution of papillomavirus-induced warts in rabbits

Abstract

We previously found that regression of skin warts induced by the Shope cottontail rabbit papillomavirus in New Zealand White rabbits, as well as malignant conversion of persistent warts, are linked to a restriction fragment length polymorphism of the major histocompatibility complex class II DRα and DQα genes. To find out whether this immunogenetic control could be connected with the antigen binding and presentation function of the α1 domain of class II molecules, we have sequenced the exon 2 of the four DRα EcoRI and six of the seven DQα PvuII restriction fragment length polymorphism alleles identified, and deduced the encoded amino acid sequences. We found no amino acid polymorphism among DRα alleles, indicating that the α1 domain of the DRα chain does not condition wart regression or cancer development. In contrast, 27 of the 82 amino acids of the DQα1 domain were found variable, defining five amino acid sequence alleles. The restriction fragment length polymorphism allele linked to regression and another allele not linked to regression share the same α1 domain, indicating that wart regression is rather conditioned by a closely linked gene. The most divergent DQα1 allele, however, was that associated with a higher risk of cancer. Alignment of rabbit and human DQα exon 2 alleles disclosed that amino acid charge variations occur at positions assumed to be important for peptide binding in humans. By modulating the affinity for tumor-specific antigenic peptides, such transitions could affect immune surveillance and, thus, condition the risk for progression to carcinoma of papillomavirus-associated lesions. © 1994.