The present invention relates to CD82 polypeptides of the mammalian tetraspanin CD82 protein family for use in the diagnosis, prevention and/or treatment of xenograft recognition and/or rejection. The present invention furthermore relates to CD82 knockout and transgenic animals and their cells, tissues and organs. The present invention furthermore relates to antibodies against a CD82 polypeptide, pharmaceutical compositions comprising at least one inhibitor of a CD82 polypeptide or comprising cells, tissues and organs of animals in which the CD82 level, expression and/or activity is modified, and their use in the diagnosis, prevention and/or treatment of xenograft recognition and/or rejection. The present invention furthermore relates to methods of diagnosing xenograft recognition and/or rejection and methods for the prevention and/or treatment of xenograft recognition and/or rejection as well as methods of xenotransplantation.