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Structural and electrostatic analysis of HLA B-cell epitopes: inference on immunogenicity and prediction of humoral alloresponses

Mallon, Dermot H.a; Bradley, J.A.a; Taylor, Craig J.b; Kosmoliaptsis, Vasilisa

Current Opinion in Organ Transplantation: August 2014 - Volume 19 - Issue 4 - p 420–427
doi: 10.1097/MOT.0000000000000108
HISTOCOMPATIBILITY: Edited by RenE J. Duquesnoy

Purpose of review: The immunogenic capacity of donor human leukocyte antigen (HLA) to induce humoral immune responses is not an intrinsic property of the mismatched alloantigen but depends on the HLA phenotype of the recipient. In recent years, advances in molecular sequence technology and information from X-ray crystallography have enabled structural comparison of donor and recipient HLA type providing an opportunity for a more rational approach for determining HLA compatibility. In this article, we review studies investigating the molecular basis of antibody–antigen interactions and present computational approaches to determine the complex physiochemical and structural properties of B-cell epitopes.

Recent findings: The relative immunogenicity of individual HLA mismatches may be predicted from analysis of polymorphic amino acids at continuous and discontinuous HLA sequence positions. The use of alloantigen sequence information alone, however, provides limited insight into key determinants of B-cell epitope immunogenicity, such as the orientation, accessibility and physiochemical properties of amino acid side chains. Advances in computational molecular modelling techniques now enable assessment of HLA-alloantibody interactions at the atomic level. Recent evidence supports a strong link between HLA B-cell epitope surface electrostatic potential and their immunogenicity.

Summary: Assessment of the surface electrostatic properties of HLA alloantigens and computational analyses of HLA-alloantibody interactions represent a promising area for future research into the molecular basis of HLA immunogenicity and antigenicity.

aDepartment of Surgery, University of Cambridge, and NIHR Cambridge Biomedical Research Centre

bTissue Typing Laboratory, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK

Correspondence to Vasilis Kosmoliaptsis, Department of Surgery, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK. Tel: +44 1223 761 337; fax: +44 1223 962 523; e-mail: vk256@cam.ac.uk

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins