REACTIVITY OF HUMAN MONOCLONAL HLA ANTIBODIES WITH PORCINE LYMPHOCYTES.
A Mulder, JGS Niterink, M Kardol, GMT Schreuder, IIN Doxiadis and FHJ Claas. Leiden University Medical Center, Department of Immunohaematology and Bloodbank, Leiden , the Netherlands, and SVM-Foundation for the Advancement of Public Health and Environmental Protection, Bilthoven, the Netherlands.

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The presence of natural antibodies, directed against the carbohydrate epitope Gal alpha1-->3Gal beta1-->4GlcNAc-R, in the human circulation is a major obstacle for porcine-to-human organ transplantation. As a consequence, the reactivity of antibodies in human sera with porcine MHC cannot be studied without extensive absorptions. We exploited our locally produced human monoclonal HLA antibodies (HLA-HuMAbs) to circumvent this problem, and performed a checkerboard analysis of 68 HLA-class I HuMAbs against 15 porcine lymphocyte suspensions by complement mediated cytotoxicity. We observed the following reactivity patterns: (i) non-reactivity of the majority (n=62) of HLA-HuMAbs, which comprises reagents directed against single alleles of HLA-A, B and C locus, (ii) four HLA HuMAbs with broad A-locus specificities, reacted with all porcine lymphocytes tested, and (iii) two HLA-HuMAbs with very broad A-locus specificities reacted with porcine lymphocytes in a polymorphic manner. Whether these reactivities are directed against porcine MHC-class I (SLA) molecules remains to be determined by ELISA-type assays.

This study demonstrates that epitopes present on cell surface proteins of porcine lymphocytes are reactive with human HLA antibodies, and can be the targets of humoral attack if HLA sensitized individuals are transplanted with porcine organs.