POSITIVE SELECTION OF T-LYMPHOCYTES ON FIBROBLASTS

THYMOCYTES are selected for expression of alphabeta T-cell antigen receptors (TCR) which recognize antigen in conjunction with self-major histocompatibility complex (MHC) molecules1,2. In the thymus the restriction element is imprinted on radioresistant stromal elements3-7 and on cells of haematopoietic origin8-10. In mice negative for beta2-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 Vbeta distribution. Here we show that in TCR-transgenic mice, intrathymic injection of L cells expressing the selecting H-2K(b) molecule (L-K(b) cells) reconstitutes the maturation of thymocytes bearing the- transgenic TCR, and that in normal B10.BR (H-2k) 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 origin3-10.