Characterization of a new HLA-B18 allele, B*1806, which lacks expression of the Bw6 epitope

HLA-B18 is a well defined Bw6-associated serologic specificity. Up to now, four different sequences have been characterised in Caucasian populations (B*1801,3,4,5), and one in Orientals (B*1802). We report a new HLA-B18 subtype (B*1806) which was serologically detected in a Spanish Caucasian individual as a B18 Bw4-associated antigen. Complete coding region sequencing showed that B*1806 differs from B*1801 in a unique nucleotide at position 299 (A to T), giving rise to an amino acid replacement in residue 76 (glutamic acid to valine) placed at the alpha1 domain. Therefore, in contrast to the serologic results, B*1806 possesses the canonical Bw6 motif at position 77-83. Subsequent flow cytometric assays proved that B*1806 evidences neither Bw4 nor Bw6 epitopes. Only three additional HLA-B alleles encode valine at codon 76, B*4601, B*7301 and B*5503, and like B*1806, all of them would include a Bw6 motif associated to the negative recognition by Bw6 antibodies. These findings support that valine at position 76 will modify the Bw6 epitope drastically, and suggest that this group of HLA-B alleles would define a third, Bw4 and Bw6-negative, lineage of molecules. Furthermore, valine 76 will also prevent the binding of Bw6 antibodies to those HLA-C antigens with the canonical Bw6 epitope (Cw*1,3,7,8,12,13,14,16).