Human HLA-DQ beta chain presents minor lymphocyte stimulating locus gene products and clonally deletes TCR V beta 6+, V beta 8.1+ T cells in single transgenic mice.
Minor lymphocyte stimulating locus (Mls) gene products in association with mouse major histocompatibility complex (MHC) class II molecules are known to determine the repertoire of T-cell receptor (TCR) in mature T cells. In order to test whether human class II molecules can present mouse Mls, HLA-DQ beta transgenic mice were generated. The expression and function of the DQ beta transgene were studied in the progeny of one selected founder which was H-2f and H-2E negative. In these mice, DQ beta molecules pairing with mouse A alpha chain and invariant chain are expressed on the cell surface in a tissue-specific manner. When the DQ beta gene was bred into the Mls-1a strain DBA/1 (H-2q), T cells bearing V beta 6 and V beta 8.1 TCR were clonally deleted in the thymus of DQ beta+ transgenics but not in DQ beta-negative full sibs. Thus, the data presented here clearly demonstrate that the human MHC DQ beta chain can present Mls in the clonal deletion of T cells. Our results also suggest the requirement for an interaction between CD4 and class II molecules (alpha chain) for clonal deletion of T cells to occur.
Zhou
P
P
Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905.
Anderson
G D
GD
Savarirayan
S
S
Inoko
H
H
David
C S
CS
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D002874:Chromosome Mapping; D005434:Flow Cytometry; D015870:Gene Expression; D006683:HLA-DQ Antigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D059866:HLA-DQ beta-Chains; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D016747:Minor Lymphocyte Stimulatory Antigens; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000378:metabolism; D014161:Transduction, Genetic
D000954:Antigens, Surface; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C057615:HLA-DQbeta antigen; D000949:Histocompatibility Antigens Class II; D016747:Minor Lymphocyte Stimulatory Antigens; D011948:Receptors, Antigen, T-Cell