Unexpected Bw4 and Bw6 reactivity patterns in new alleles

Abstract

The Bw4 and Bw6 epitopes were the first HLA-B differences to be recognized by serological methods. Since then 44 serological groups have been identified and more than 250 alleles assigned by molecular typing methods. In general each serological HLA-B group is associated with the presence of either the Bw4 or the Bw6 epitope. There are several exceptions to this rule. Four alleles, B*4601, *7301, *5503 and *1806, show no serological reactivity with either Bw4 or Bw6. Although the Bw6 motif at residues 77-83 is present in these alleles the Bw6 epitope is modified by a valine at residue 76. One or more alleles from the B8, B40 and B62 groups are identified as Bw4 positive, whereas all others are Bw6 positive. In the groups B27, B44 and B47 several alleles are found to be Bw6 positive, while the majority is Bw4 positive. Histocompatibility testing of dialysis patients and their families revealed the serological presence of an unexpected Bw4 epitope associated with B18 in one patient and B56 in another. Allele-specific amplification and sequencing of exons 2 and 3 of these HLA-B alleles revealed the presence of the Bw4 sequence motif for both. The new alleles were assigned B*1809 and B*5607, respectively. In 2 other patients the presence of a new B*07 allele was determined by sequence based typing. Although the new allele, B*0715, showed the Bw6 sequence motif at positions 77 to 83, a substitution of amino acid 76 from glutamic acid to valine was identified. This change resulted in an aberrant Bw6 serological reaction pattern.

High-resolution, three-dimensional modeling of human leukocyte antigen class I structure and surface electrostatic potential reveals the molecular basis for alloantibody binding epitopes

“…For example, HLA-B*44:02, B*56:07, B*08:02, and B*18:09 have identical amino acid sequences at positions 77-83 that encompasses the Bw4 epitope, but that Bw4-specific antibodies bind strongly to B*44:02 and B*56:07 but only weakly to B*08:02 and B*18:09 (Fig. 4) [30,33]. The electrostatic models of the Bw4 epitope carried on the above four HLA alleles provide a likely explanation, revealing that amino acid polymorphisms outside the Bw4 motif, alter the electrostatic pattern and structural context of the Bw4 epitope (Fig.…”

“…The majority of HLA alleles that express the Bw4 epitope incorporate the motifs T-A-L-R, I-A-L-R, and T-L-L-R at positions 80 -83, and asparagine, serine, or aspartic acid at position 77 [30]. Differences in Bw4 specific alloantibody binding patterns are well documented among HLA specificities that express the Bw4 epitope [31,32].…”

New insights of HLA class I association to Behçet’s disease in Portuguese patients

“…The KIR genes possessing two intracellular domains are mainly specific for HLA‐Cw specificities. Another member of this group of receptors binds residues 77–83 of HLA‐B alleles that have been designated Bw4 by serology and are shared by the B*51 allele (24).…”

A MAGE‐3 peptide presented by HLA‐B44 is also recognized by cytolytic T lymphocytes on HLA‐B18

“…This implies that the clinical use of peptide MEVDPIGHLY, presently restricted to B44 patients, can now be extended to B*1801 patients. Human leukocyte antigen allelic group B18 comprises nine alleles, which are expressed by a total of 6% of Caucasians (36, 37). Furthermore, we cannot exclude the possibility that peptide MEVDPIGHLY binds to other B18 molecules.…”