Nucleotide sequence analysis of the C.AKR Lyt-2 agene: structural polymorphism in alleles encoding the Lyt-2.1 T-cell surface alloantigen

The Lyt-2 ^aallele of the C.AKR strain of mice (genotype Lyt-2 ^a, Lyt-3 ^a) was cloned, and its complete nucleotide sequence as well as that of 2 kb of 5 flanking DNA was determined. The sequence was comapred with the partial sequence of the Lyt-2 ^aallele of DBA/2 (genotype Lyt-2 ^a, Lyt-3 ^b) and the nearly complete sequence of the B10.CAS2 Lyt-2 ^ballele reported by Liaw and coworkers (1986). The coding regions of the two Lyt-2 ^aalleles differ from each other by two nucleotide substitutions in the three exons over which they could be compared, resulting in two amino acid substitutions in the leader and transmembrane segments. The coding region of the C.AKR Lyt-2 ^aallele differs from the Lyt-2 ^ballele by two nucleotide substitutions in the extracellular V-like domain, one of which is silent and the second of which leads to substitution of valine for methionine at amino acid position 78 giving rise to the Lyt-2.1 allotypic specificity. The coding region of the DBA/2 Lyt-2 ^aallele shares with C.AKR the allotypic substitution at position 78 and differs from Lyt-2 ^bby three additional nucleotide substitutions in the coding regions, two of which lead to amino acid substitutions in the leader and transmembrane segments. It would therefore appear that the Lyt-2 alleles of the three strains analyzed are distinct, and the nomenclature Lyt-2 ^a1 and Lyt-2 ^a2 is suggested to distinguish the alleles of C.AKR and DBA/2, respectively. These alleles share a common difference from the Lyt-2 ^bgene product at position 78, and since the amino acid substitutions which distinguish them from each other are in the leader and transmembrane segments, their mature Lyt-2 gene products appear antigenically identical.