Positive selection of T-lymphocytes induced by intrathymic injection of a thymic epithelial cell line

Abstract

T LYMPHOCYTES recognize antigens as peptide fragments associated with molecules encoded by the major histocompatibility complex (MHC) and expressed on the surface of antigen-presenting cells¹. In the thymus, T cells bearingαβ receptors that react with the MHC molecules expressed by radioresistant stromal elements are positively selected for maturation^2–5. In (A × B → A) bone marrow chimaeras, T cells restricted to the MHC-A haplotype are positively selected, whereas MHC-B-reactive thymocytes are not. We investigated whether the introduction of particular thymic stromal elements bearing MHC-B molecules could alter the fate of B-reactive T cells in these (A × B → A) chimaeras. Thymic epithelial cell (TEC) lines expressing H−2^b were introduced by intrathymic injection into (H−2^b/s → H2^S) bone marrow chimaeras and we measured their ability to generate H−2^b-restricted cytotoxic T-lymphocytes (CTLs). We report here that one TEC line, 427.1, was able positively to select CTLs specific for influenza and vesicular stomatitis virus antigens in association with class I H−2^bmolecules. In addition, line 427.1 can process cytoplasmic proteins for presentation to H−2K^b- and H−2D^b-restricted CTLs. Thus, a TEC line capable of normal class I MHC antigen processing and presentation in vitro can induce positive selection after intrathymic injection.