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 selection events was investigated using transgenic mice. Both GPI-D^b and TM-D^b can efficiently present H-Y antigen, influenza and lymphocytic choriomeningitis virus (LCMV) peptides to primed cytotoxic. H-2D^b-restricted T cells. Transgenic mice expressing GPI-D^b, although unable to reject TM-D^b skin grafts, nevertheless generate secondary CTL responses 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 cells. This paradoxical behaviour of GPI-D^b molecules suggests that the structural requirements for antigen presentation and thymic selection by class I molecules are different and may explain why GPI-linked class I molecules, such as Qa-2, do not appear to function as restriction elements in vivo.