Positive selection of T lymphocytes on fibroblasts

Abstract

THYMOCYTES are selected for expression of αβ T-cell antigen receptors (TCR) which recognize antigen in conjunction with self-major histocompatibility complex (MHC) molecules^1,2. In the thymus the restriction element is imprinted on radioresistant stromal elements^3–7 and on cells of haematopoietic origin^8–10. In mice negative for β₂-microglobulin that are devoid of mature cytotoxic T lymphocytes¹¹, we find that intrathymic injection of different fibroblasts causes the maturation of CD4⁻CD8⁺TCR^high thymocytes with distinct patterns of TCR Vβ distribution. Here we show that in TCR-transgenic mice, intrathymic injection of L cells expressing the selecting (H–2K^b) molecule (H–2K^b cells) reconstitutes the maturation of thymocytes bearing the transgenic TCR, and that in normal B10.BR (H–2^k) mice, H–2K^b molecules expressed on L–K^b cells lead to the development of T lymphocytes with recognition restricted to H–2K^b. A class I MHC restriction element can thus be selected by interaction with fibroblasts, that is, cells of other than epithelial or haematopoietic origin^3–10.