Mutations in the major histocompatibility complex class I antigen-presenting groove affect both negative and positive selection of T cells.
In several transgenic mouse models T cell development was shown to be controlled by the binding of the alpha/beta T cell receptor (TcR) to ligands in the thymus. In transgenic mice expressing a male-specific TcR alpha/beta, the presence of the restricting D major histocompatibility complex (MHC) molecule plus the male specific peptide deleted thymocytes at an early stage of development. On the other hand, maturation of T cells required an interaction of the TcR with the thymic D MHC molecules in the absence of specific peptides. This could imply that negative and positive selection of this receptor are affected differently by mutations in the HY peptide-binding groove of the D MHC molecule. Such mutants have been isolated and were shown to affect the response to HY antigen in that both the bm14 (residue Glu70----Asp) and the bm13 (residue Leu114----Glu, Phe116----Tyr and Glu119----Asp) strains do not normally mount cytotoxic responses to male cells. Here we show that these mutations affect antigenicity of male cells, as well as negative and positive selection of T cells in TcR alpha/beta transgenic mice.
Jacobs
H
H
Division of Molecular Genetics, University of Amsterdam.
Von Boehmer
H
H
Melief
C J
CJ
Berns
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D005260:Female; D005434:Flow Cytometry; D006182:H-Y Antigen / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012727:Sex Characteristics; D013154:Spleen / Q000166:cytology / Q000528:radiation effects; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology
D000911:Antibodies, Monoclonal; D006182:H-Y Antigen; D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta