IDENTIFICATION OF A NEW BOVINE MHC CLASS-II DRB ALLELE BY NUCLEOTIDE SEQUENCING AND AN ANALYSIS OF PHYLOGENETIC-RELATIONSHIPS

Three overlapping cDNA clones coding for the bovine major histocompati bility complex (MHC) class II DR beta chain were isolated. A clone NR1 encoded a primary translated product of 266 amino acids, 29 of which were deduced to form a signal peptide and 237 to form the mature polyp eptide. The protein predicted from this cDNA appeared to have all the features expected of an expressed MHC class II molecule. Comparison of the sequences and construction of a phylogenetic tree revealed that N R1 represents a BoLA-DRB3 gene and not a BoLA-DRB1 or BoLA-DRB2 pseudo gene. NR1 and ovine sequences exhibited the greatest overall similarit y among sequences from various mammalian species, followed by the equi valent human sequences. Indeed, the bovine allele was more closely rel ated to certain ovine alleles than to other bovine alleles. A large nu mber of replacement substitutions were identified when pi domains enco ded by NR1 and each of the 36 distinct BoLA-DRB3 alleles were compared , and most of the allelic variations were found in regions that are co mmonly polymorphic in DRB sequences from different species and corresp ond to the predicted antigen-recognition sire. Thus, the predicted str ucture of the unique NR1 allele for BoLA-DRB3 further confirms the ove rall conservation of the product of this locus, as previously establis hed from studies in rodent and man. (C) 1995 Academic Press, Inc.