Metallothioneins (MTs) are small cysteine‐rich proteins whose structure is conserved from fungi to man. MTs strongly bind heavy metals, notably zinc, copper and cadmium. Upon exposure of cells to heavy metal and other adverse treatments, MT gene transcription is strongly enhanced. Metal induction is mediated by several copies of a 15 bp consensus sequence (metal‐responsive element, MRE) present in the promoter region of MT genes. We and others have demonstrated the presence of an MRE‐binding factor in HeLa cell nuclear extracts. We found that this factor, termed MTF‐1 (MRE‐binding transcription factor) is inactivated/reactivated in vitro by zinc withdrawal/addition. Here we report that the amounts of MTF‐1‐DNA complexes are elevated several‐fold in zinc‐treated cells, as measured by bandshift assay. We have also cloned the cDNA of mouse MTF‐1, a 72.5 kDa protein. MTF‐1 contains six zinc fingers and separate transcriptional activation domains with high contents of acidic and proline residues. Ectopic expression of MTF‐1 in primate or rodent cells strongly enhances transcription of a reporter gene that is driven by four consensus MREd sites, or by the complete mouse MT‐I promoter, even at normal zinc levels.

B LYMPHOCYTES are key participants in the immune response because of their specificity, their ability to take up and present antigens to T cells, and their capacity to differentiate into antibody-secreting cells. To limit reactivity to self antigens, autospecific B cells can be functionally inactivated or deleted. Developing B cells that react with membrane antigens expressed in the bone marrow are deleted from the peripheral lymphocyte pool. It is important to ascertain the fate of B cells that recognize membrane autoantigens expressed exclusively on peripheral tissues because B cells in the peripheral lymphoid organs are phenotypically and functionally distinct from bone-marrow B cells. Here we show that in immunoglobulin-transgenic mice, B cells specific for major histocompatibility complex class I antigen can be deleted if they encounter membrane-bound antigen at a post-bone-marrow stage of development. This deletion may be necessary to prevent organ-specific autoimmunity.

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T-cell receptor alpha- and beta-chain genes were isolated from a class I major histocompatibility complex-restricted cytotoxic T-cell clone and transferred by protoplast fusion into another cytolytic T-cell clone of different specificity. Expression of the transfected alpha and beta genes endowed the recipient cell with the specificity of the donor cell.

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