Purpose of review: To describe the structural basis of human leukocyte antigen (HLA) Bw4 and Bw6 epitopes that are recognized by antibodies and the KIR3DL1 natural killer cell receptor.
Recent findings: Molecular modeling and X-ray crystallography have refined our understanding of Bw4 and Bw6. These epitopes had been defined by comparison of HLA allele sequences and by site-directed mutagenesis. Anti-Bw4 and anti-Bw6 antibodies and KIR3DL1 receptors recognize HLA α-1 α-helix residues 77–83 in combination with other HLA regions. The variability of HLA sequences within the 77–83 region and at other sites indicates that the Bw4 epitope is complex. Adding complexity, HLA-bound peptides influence Bw4 and Bw6 epitopes. These structures are recognized by diverse antibodies and KIR3DL1 allotypes. This diversity allowed a Bw4+ patient to produce anti-Bw4 antibody without breaking self-tolerance.
Summary: Bw4 and Bw6 epitopes are best regarded as families of related structures that are recognized by a diverse array of antibodies and KIR3DL1 allotypes.