The major barrier to clinically successful pig-to-human xenotransplantation
is antibody- and complement-dependent hyperacute rejection, known to be du
e to host antiGal alpha(1,3)Gal antibodies. Strategies aimed at eliminating
hyperacute rejection involve transgenic approaches to eliminate or reduce
expression of Gal alpha(1,3)Gal or to reduce complement activation; some of
these are now in clinical trials in primates. Another important role of Ga
l alpha(1,3)Gal that is becoming more evident is in antibody-dependent and
-independent xenograft rejection that is mediated by natural killer cells a
nd monocytes.