title: Mixed-haplotype MHC class II molecules select functional CD4+ T cells.
abstract: MHC class II molecules are formed from polymorphic alpha and beta chains. While pairing of chains is most efficient within class II isotypes and haplotypes, limited pairing and surface expression of mixed-haplotype and -isotype class II molecules is common. The function of such molecules in antigen presentation has been established by the unique restriction of responses in F1 mice. However, it has not been established whether mixed class II molecules are able to mediate selection of functional T cells and how the reduced avidity of the TCR/MHC interaction influences the repertoire. In this report we have addressed these issues through the production of mice expressing solely mixed-haplotype class II molecules. The mixed class II molecules promote selection of a small CD4+ T cell repertoire with modified TCR use. The selected CD4+ T cells are functional in vivo and in vitro.
authors.affiliation: Transplantation Biology Group, Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Silk
authors.forename: Diana
authors.initials: D
authors.lastname: Schoendorf
authors.forename: Istvan
authors.initials: I
authors.lastname: Bartok
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Chai
authors.forename: David
authors.initials: D
authors.lastname: Gray
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Simpson
authors.forename: Julian
authors.initials: J
authors.lastname: Dyson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology; D001854:Bone Marrow Cells; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D003433:Crosses, Genetic; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005434:Flow Cytometry; D005720:Gamma Rays; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006239:Haplotypes / Q000235:genetics* / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D012641:Selection, Genetic; D017386:Sequence Homology, Amino Acid; D016038:Skin Transplantation / Q000276:immunology; D013154:Spleen / Q000166:cytology
chemical_list: D000911:Antibodies, Monoclonal; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; D016178:Granulocyte-Macrophage Colony-Stimulating Factor