Positive selection of CD4+ thymocytes controlled by MHC class II gene products

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Abstract
The mature T-cell antigen receptor repertoire is characterized by lack of reactivity to self-components as well as by preferential reactivity to foreign antigens in the context of polymorphic self-proteins encoded within the major histocompatibility complex1. Whereas the former characteristic (referred to as negative selection or tolerance) is associated with intrathymic deletion of T cells expressing T-cell antigen receptor β-chain variable domains, which confer a preferential reactivity to self antigens2–4, the existence of the latter (referred to as positive selection or MHC restriction) has so far only been inferred indirectly from functional studies5–8. We show here that intrathymic deletion of V+ β6T cells (reactive with a self-antigen encoded by the Mls a locus) is control-led by polymorphic MHC class II determinants. Furthermore, in mice lacking expression of Mls *, the same class II MHC loci control the frequency of occurrence of V+ β6cells among mature CD4+ T lymphocytes. These data are direct evidence for positive selection by MHC determinants in the thymus in unmanipulated animals.