The objective of this study is to describe the gene characteristics of the bovine lymphocyte antigen (BoLA)-DQB exon 2 locus in Chinese yakow (Bos grunniens × Bos taurus) and to compare it with previously reported patterns in other bovidae species to investigate genetic factors for disease resistance. The exon 2 of the MHC class II DQB gene was cloned and sequenced. It was revealed by sequence analyses that there are 36 DQB exon 2 alleles among 44 Chinese yakow. These alleles exhibited a high degree of nucleotide and amino acid polymorphism with most amino acid variations occurring at positions forming the peptide-binding sites (PBS). The DQB loci were analysed for patterns of synonymous (dS) and nonsynonymous (dN) substitution. The Chinese yakow was observed to be under strong positive selection in the DQB exon 2 peptide-binding sites (dN = 0.147, P < 0.01). It appears that this variability among Chinese yakow confers the ability to mount immune responses to a wide variety of peptides or pathogens.