Athymic mice express a high level of functional γ-chain but greatly reduced levels of α- and β-chain T-cell receptor messages

Abstract

T lymphocytes differentiate and mature in the thymus. It is here that thymocytes with reactivities to self antigens are eliminated and those with specificities to ‘altered’ self-major histocompatibility complex (MHC) gene products are positively selected¹. The selections are presumably carried out on the basis of their T-cell antigen receptors (TcR). The genes of the α- and β-chain T-cell antigen receptors have been cloned^2–7. A third T-cell specific gene capable of undergoing somatic rearrangement has also been identified⁸; the role of this third gene is not known. An order of expression of γ, β, then α is found during T-cell ontogeny^9,10. But although α- and β-chain messages are often functional^11–15, γ transcripts are rarely functional in thymocytes or mature T cells^16–18. To define the sequential order of expression of these genes further and to continue the search for a possible role for the TcR γ gene products, we investigated the expression of ‘functional’ α-, β- and γ-chain transcripts in young athymic mice. These mice express an undetectable amount (less than one in 8 × l0⁵ spleen messages) of ‘full-length’ α- and β-chain T-cell receptor transcripts, but an increased level of expression of ‘full-length’ γ chain messages. Nucleotide sequence analysis of four γ complementary DNAs show that all four γ transcripts sequenced are functional. These findings suggest that γ gene products may be important in a prethymic or extrathymic pathway and may represent a second type of T-cell recognition, possibly in a lineage in which α and β genes are not used.