ABSTRACT
Naturally occurring antibodies (i.e., those existing without known exogenous antigen stimulation) are fundamental in the response to foreign organisms and function in both innate and adaptive immune responses. Indeed, natural preformed antibodies in a recipient are the ˆrst immunological barrier for clinical transplantation. To overcome the chronic shortage of organs available for transplantation, the practice of live donation across the ABO blood group barrier is now performed in many countries (Nydegger et al. 2005; Wu et al. 2003). Furthermore, pig-to-human xenotransplantation is also being investigated as a viable solution. However, without intervention, the recipient’s natural antibodies would cause hyperacute rejection of the graft. These natural antibodies recognize carbohydrate epitopes on the donor tissue (A or B blood group antigens for allotransplantation; Galα(1-3)Gal [αGal] for xenotransplantation),
9.1 Introduction .................................................................................................. 215 9.2 Natural Antibodies and Their Antigens ....................................................... 216
9.2.1 The ABO Blood Groups ................................................................... 216 9.2.2 The αGal Xenoantigen ...................................................................... 216 9.2.3 Target Antigens for Natural Antibodies ........................................... 217 9.2.4 Anti-αGal Monoclonal Antibodies ................................................... 218 9.2.5 Anti-αGal Antibody Genes .............................................................. 218 9.2.6 Anti-αGal Antibody Structure ......................................................... 219 9.2.7 Anti-αGal Antibody Responses ........................................................220 9.2.8 Clinical Relevance of Anti-αGal Antibodies ................................... 222
9.3 Glycosyltransferases ..................................................................................... 222 9.3.1 Human A and B Transferases ........................................................... 223 9.3.2 αGT ...................................................................................................224 9.3.3 iGb3S ................................................................................................226
