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Identification of the V H genes encoding xenoantibodies in non‐immunosuppressed rhesus monkeys
Author(s) -
Kleihauer Annette,
Gregory Clare R.,
Borie Dominic C.,
Kyles Andrew E.,
Shulkin Irina,
Patanwala Insiyyah,
ZahorskyReeves Joanne,
Starnes Vaughn A.,
Mullen Yoko,
Todorov Ivan T.,
KearnsJonker Mary
Publication year - 2005
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2005.02204.x
Subject(s) - xenotransplantation , biology , germline , antibody , gene , microbiology and biotechnology , immune system , transplantation , immunology , genetics , medicine , surgery
Summary The major immunological barrier that prevents the use of wild‐type pig xenografts as an alternative source of organs for human xenotransplantation is antibody‐mediated rejection. In this study, we identify the immunoglobulin variable region heavy (IgV H ) chain genes encoding xenoantibodies to porcine heart and fetal porcine islet xenografts in non‐immunosuppressed rhesus monkeys. We sought to compare the IgV H genes encoding xenoantibodies to porcine islets and solid organ xenografts. The immunoglobulin M (IgM) and IgG xenoantibody response was analysed by enzyme‐linked immunosorbent assay and cDNA libraries from peripheral blood lymphocytes were prepared and sequenced. The relative frequency of IgV H gene usage was established by colony filter hybridization. Induced xenoantibodies were encoded by the IGHV3‐11 germline progenitor, the same germline gene that encodes xenoantibodies in humans mounting active xenoantibody responses. The immune response to pig xenografts presented as solid organs or isolated cells is mediated by identical IgV H genes in rhesus monkeys. These animals represent a clinically relevant model to identify the immunological basis of pig‐to‐human xenograft rejection.