Abstract
AbstractAntibodies reactive to human leukocyte antigens (HLA) represent a barrier for patients awaiting transplantation. Based on reactivity patterns in single-antigen bead (SAB) assays, various epitope matching algorithms have been proposed to improve transplant outcomes. However, some antibody reactivities cannot be explained by amino acid motifs, leading to uncertainty about their clinical relevance. Antibodies against the HLA class II molecule, DQβ0603:DQα0103, present in some candidates, represent one such example. Here, we show that peptides derived from amino acids 119-148 of the HLA class I heavy chain are bound to DQβ0603:DQα0103 proteins and contribute to antibody reactivity through an HLA-DM-dependent process. Moreover, antibody reactivity is impacted by the specific amino acid sequence presented. In summary, we demonstrate that polymorphic HLA class I peptides, bound to HLA class II proteins, can directly or indirectly be part of the antibody binding epitope. Our findings have potential important implications for the field of transplant immunology and for our understanding of adaptive immunity.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference30 articles.
1. Patel, R. & Terasaki, P. I. Significance of the positive crossmatch test in kidney transplantation. N. Engl. J. Med 280, 735–739 (1969).
2. Fuller, T. C., Fuller, A. A., Golden, M. & Rodey, G. E. HLA alloantibodies and the mechanism of the antiglobulin-augmented lymphocytotoxicity procedure. Hum. Immunol. 56, 94–105 (1997).
3. Garovoy, M. R. et al. Flow cytometry analysis: a high technology cross-match technique facilitating transplantation. Transpl. Proc. 15, 1939–1944 (1983).
4. Pei, R., Lee, J.-H., Shih, N.-J., Chen, M. & Terasaki, P. I. Single human leukocyte antigen flow cytometry beads for accurate identification of human leukocyte antigen antibody specificities. Transplantation 75, 43–49 (2003).
5. Friedewald, J. J. et al. The kidney allocation system. Surg. Clin. North Am. 93, 1395–1406 (2013).