HLA-B21 is not an epitope, but a cluster of different epitopes

Abstract

Aim Definition of the anti-HLA-B21 antibody specificity in terms of amino acid sequence properties of the target alleles. Methods Antibody specificities are analysed using single-antigen beads by One Lambda. We define an epitope as a set of amino acid positions that could account for the interaction of HLA alleles with anti-HLA antibodies. We call ‘isoforms’ the amino acid variations at those positions encountered in clinical antibody specificities. A propositional logic algorithm is used to minimise the number of epitopes and maximise the number of clinical antibody specificities accounted for by each epitope. In defining an epitope, some of its isoforms are associated with known antibody specificities, the rest are presumed antibody specificities not yet identified. Results The search for the molecular characterisation of B21 led to the identification of the complex epitope defined by amino acid positions 113, 114, 116, 152, 156 and 163. The isoforms of this epitope include the following well-known HLA-B specificities: B18, B7, B16, B82, B13, B5, B44, B14, B37, B73, B45 and a restricted form of B21. In addition, this epitope accounts for the following additional antibody specificities: [B27+B47], [B40+B48+B81], [B8+B41+B42], [B22+B59] and [B35+B53+B58+B5701], some of which have been confirmed empirically. In spite of its explanatory and predictive power, this epitope does not account for the classical B21 serologic specificity, but for the restricted B21 specificity including B49 and B50. The classical [B49+B50+B4005] B21 specificity is accounted for by the epitope defined by amino acid positions 24, 32, 152, 156 and 163. In addition, the isolated specificities [B50+B4005] and [B49] are explained by positions 24, 32, 77, 152, 156 and 163; and the [B50] specificity by itself by positions 77, 113, 114 and 116. Conclusion The classical serologic specificity B21 is not a unique specificity but a cluster of multiple specificities associated with B49 and B50 and defined by different epitopes. One epitope accounts for multiple serologic specificities, and what we call one specificity is accounted for by multiple epitopes. It is important to clarify conceptually what epitopes and serologic specificities are.