SEPARATION OF THYMIC EDUCATION FROM ANTIGEN-PRESENTING FUNCTIONS OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I MOLECULES

Participation of transmembrane (TM) and glycosyl-phosphatidylinositol (GPI) anchored H-2D(b) molecules in antigen presentation and thymic se lection events was investigated using transgenic mice. Both GPI-D-b an d TM-D-b can efficiently present H-Y antigen, influenza and lymphocyti c choriomeningitis virus (LCMV) peptides to primed cytotoxic, H-2D(b)- restricted T cells. Transgenic mice expressing GPI-D-b, although unabl e to reject TM-D-b skin grafts, nevertheless generate secondary CTL re sponses which can lyse TM-D-b-bearing targets, indicating that GPI-D-b mice fail to delete all TM-D-b-reactive T cells. Furthermore, double- transgenic mice bearing GPI-D-b and a T-cell receptor (TcR) for H-2D(b ) + LCMV do not positively select receptor positive, CD8(+)CD4(-) T ce lls. This paradoxical behaviour of GPI-Db molecules suggests that the structural requirements for antigen presentation and thymic selection by class I molecules are different and may explain why GPI-linked clas s I molecules, such as Qa-2, do not appear to function as restriction elements in vivo.