T cell repertoire formation displays characteristics of qualitative models of thymic selection.
The use of T cell receptor elements varies between mouse strains, reflecting a balance between positive and negative selection. The presence of H-2E biases V alpha and V beta usage through major histocompatibility class II isotype preferences of V elements, and mammary tumor virus-dependent, negative selection. Quantitative models of thymic selection predict that negative selection equates to 'excess' positive selection, whereas qualitative models suggest that positive and negative selection are opposing forces. This report attempts to distinguish between the models by assessing whether, at the level of the T cell repertoire, positive and negative selection have quantitative or qualitative characteristics. The data show that the effect of bearing V alpha and V beta regions which are both preferentially (or negatively) selected in the presence of H-2E is additive or synergistic, whilst positive stimuli counteract negative ones. The data thus provide support for qualitative models of thymic selection.
Elliott
J I
JI
Transplantation Biology Group, Clinical Sciences Center, Hammersmith Hospital, London, GB.
D000818:Animals; D006183:H-2 Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D008954:Models, Biological; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D006183:H-2 Antigens; D006684:HLA-DR Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta