title: Separation of thymic education from antigen presenting functions of major histocompatibility complex class I molecules.
abstract: Participation of transmembrane (TM) and glycosyl-phosphatidylinositol (GPI) anchored H-2Db molecules in antigen presentation and thymic selection events was investigated using transgenic mice. Both GPI-Db and TM-Db can efficiently present H-Y antigen, influenza and lymphocytic choriomeningitis virus (LCMV) peptides to primed cytotoxic, H-2Db-restricted T cells. Transgenic mice expressing GPI-Db, although unable to reject TM-Db skin grafts, nevertheless generate secondary CTL responses which can lyse TM-Db-bearing targets, indicating that GPI-Db mice fail to delete all TM-Db-reactive T cells. Furthermore, double-transgenic mice bearing GPI-Db and a T-cell receptor (TcR) for H-2Db+LCMV do not positively select receptor positive, CD8+CD4- T cells. 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 class I molecules, such as Qa-2, do not appear to function as restriction elements in vivo.
authors.affiliation: Clinical Research Centre, Harrow, Middlesex, U.K.
authors.forename: E
authors.initials: E
authors.lastname: Simpson
authors.forename: P J
authors.initials: PJ
authors.lastname: Robinson
authors.forename: P
authors.initials: P
authors.lastname: Chandler
authors.forename: M M
authors.initials: MM
authors.lastname: Millrain
authors.forename: H P
authors.initials: HP
authors.lastname: Pircher
authors.forename: D
authors.initials: D
authors.lastname: Brändle
authors.forename: P
authors.initials: P
authors.lastname: Tomlinson
authors.forename: J
authors.initials: J
authors.lastname: Antoniou
authors.forename: A
authors.initials: A
authors.lastname: Mellor
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D017261:Glycosylphosphatidylinositols / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D016038:Skin Transplantation / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology*
chemical_list: D017261:Glycosylphosphatidylinositols; D015395:Histocompatibility Antigens Class I