title: Negative and positive selection of antigen-specific cytotoxic T lymphocytes affected by the alpha 3 domain of MHC I molecules.
abstract: The alpha 1 and alpha 2 domains of major histocompatibility complex (MHC) class I molecules function in the binding and presentation of foreign peptides to the T-cell antigen receptor and control both negative and positive selection of the T-cell repertoire. Although the alpha 3 domain of class I is not involved in peptide binding, it does interact with the T-cell accessory molecule, CD8. CD8 is important in the selection of T cells as anti-CD8 antibody injected into perinatal mice interferes with this process. We previously used a hybrid class I molecule with the alpha 1/alpha 2 domains from Ld and the alpha 3 domain from Q7b and showed that this molecule binds an Ld-restricted peptide but does not interact with CD8-dependent cytotoxic T lymphocytes. Expression of this molecule in transgenic mice fails to negatively select a subpopulation of anti-Ld cytotoxic T lymphocytes. In addition, positive selection of virus-specific Ld-restricted cytotoxic T lymphocytes does not occur. We conclude that besides the alpha 1/alpha 2 domains of class I, the alpha 3 domain plays an important part in both positive and negative selection of antigen-specific cells.
authors.affiliation: Department of Microbiology, University of Texas Southwestern Medical Center, Dallas.
authors.forename: C J
authors.initials: CJ
authors.lastname: Aldrich
authors.forename: R E
authors.initials: RE
authors.lastname: Hammer
authors.forename: S
authors.initials: S
authors.lastname: Jones-Youngblood
authors.forename: U
authors.initials: U
authors.lastname: Koszinowski
authors.forename: L
authors.initials: L
authors.lastname: Hood
authors.forename: I
authors.initials: I
authors.lastname: Stroynowski
authors.forename: J
authors.initials: J
authors.lastname: Forman
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D016827:CD8 Antigens; D003587:Cytomegalovirus / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology*; D007111:Immunity, Cellular; D008285:Major Histocompatibility Complex; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000956:Antigens, Viral; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D014764:Viral Proteins