Bw4

Bw4 is a serologic epitope defined on a subset of human leukocyte antigen (HLA-B) class I molecules. It forms one of the two major B lineage epitopes, alongside Bw6, and is used in immunogenetics and transplantation to describe how certain HLA-B alleles are recognized by specific antibodies and receptors.

Molecular basis. The Bw4 motif is determined by a segment of the HLA-B heavy chain, with residues in the α1 domain around positions 77 to 83 contributing to the Bw4/Bw6 distinction. Within the Bw4 group, subtypes such as Bw4-80I and Bw4-80T reflect variation at residue 80, which can influence how the epitope is perceived by immune receptors. Bw4 is recognized by particular monoclonal antibodies used in serologic typing and can be distinguished from the Bw6 epitope in laboratory assays.

Interactions with natural killer cells. The Bw4 epitope engages certain killer-cell immunoglobulin-like receptors (KIRs) on natural killer (NK) cells, notably KIR3DL1 and, in some contexts, KIR3DS1. These interactions contribute to NK cell education and the regulation of killing activity, influencing innate immune responses to infected or malignant cells. The Bw4-80I variant, in particular, has been associated with higher binding affinity to KIR3DL1 in some studies.

Clinical relevance. Bw4 status is relevant in allogeneic hematopoietic stem cell transplantation, where donor-recipient matching can affect NK cell–mediated alloreactivity and graft-versus-leukemia effects. Associations have also been reported between specific Bw4/KIR combinations and the course of certain infections, such as HIV, and other immune-related outcomes, though findings can vary across populations.

See also: HLA-B, Bw6, KIR, NK cells.