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Human leukocyte antigen epitope antigenicity and immunogenicity

Duquesnoy, René J.

Current Opinion in Organ Transplantation: August 2014 - Volume 19 - Issue 4 - p 428–435
doi: 10.1097/MOT.0000000000000100
HISTOCOMPATIBILITY: Edited by RenE J. Duquesnoy

Purpose of review: Human leukocyte antigen (HLA) antibodies are now recognized as being specific for epitopes which can be defined structurally with amino acid differences between HLA alleles. This article addresses two general perspectives of HLA epitopes namely antigenicity, that is their reactivity with antibody and immunogenicity, that is their ability of eliciting an antibody response.

Recent findings: Single-antigen bead assays have shown that HLA antibodies recognize epitopes that are equivalent to eplets or corresponding to eplets paired with other residue configurations. There is now a website-based Registry of Antibody-Defined HLA Epitopes (http://www.epregistry.com.br). Residue differences within eplet-defined structural epitopes may also explain technique-dependent variations in antibody reactivity determined in Ig-binding, C1q-binding and lymphocytotoxicity assays.

HLA antibody responses correlate with the numbers of eplets on mismatched HLA antigens, and the recently proposed nonself–self paradigm of epitope immunogenicity may explain the production of epitope-specific antibodies.

Summary: These findings support the usefulness of HLA matching at the epitope level, including the identification of acceptable mismatches for sensitized patients and permissible mismatching for nonsensitized patients aimed to reduce HLA antibody responses.

Division of Transplant Pathology, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA

Correspondence to Division of Transplant Pathology, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh 15261, Pennsylvania, USA. E-mail: DuquesnoyR@upmc.edu

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins