Human leukocyte antigen Bw4 and Bw6 epitopes recognized by antibodies and natural killer cells

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.