Fragments from the 3′ end of a mouse histone H4 gene, when introduced into transcription units controlled by the SV40 early promoter, yield correctly processed RNA with histone‐specific 3′ ends, both in monkey and mouse cell lines. The processed RNA is regulated in parallel with endogenous H4 mRNAs in 21‐Tb cells, a temperature‐sensitive mouse mastocytoma cell cycle mutant that is specifically blocked in G1 phase at the non‐permissive temperature. Mutational analyses of the H4 gene fragment indicate that the minimal sequences for this regulation and for RNA 3′ processing are both contained within the same 80 bp. This fragment contains two histone‐specific, highly conserved sequence elements that are located at the 3′ end of histone mRNA and in the adjacent spacer region, respectively. Our data suggest that the observed cell cycle regulation is achieved either at RNA 3′ processing or at some later step involving the conserved 3′‐terminal sequence element of mature histone mRNA.
The gene segments encoding the constant and variable regions of human immunoglobulin light chains of the kappa type (C kappa, V kappa) have been localized to chromosome 2. The distance between the C kappa and V kappa genes and the number of germline V kappa genes are unknown. As part of our work on the human V kappa locus, we have now mapped two solitary V kappa gene and a cluster of three V kappa genes to chromosomes 1, 15 and 22, respectively. The three genes that have been sequenced are nonprocessed pseudogenes, and the same may be true for the other two genes. This is the first time that V-gene segments have been found outside the C-gene-containing chromosomes. Our finding is relevant to current estimates of the size of the V kappa-gene repertoire. Furthermore, the dispersed gene regions have some unusual characteristics which may help to clarify the mechanism of dispersion.
Although AIDS patients lose human immunodeficiency virus (HIV)-specific cytotoxic T cells, their remaining CD8-positive T lymphocytes maintain cytotoxic function. To exploit this fact we have constructed bispecific antibodies that direct cytotoxic T lymphocytes of any specificity to cells that express gpl20 of HIV. These bispecific antibodies comprise one heavy/light chain pair from an antibody to CD3, linked to a heavy chain whose variable region has been replaced with sequences from CD4 plus a second light chain. CD3 is part of the antigen receptor on T cells and is responsible for signal transduction. In the presence of these bispecific antibodies, T cells of irrelevant specificity effectively lyse HIV-infected cells in vitro.
SUMMARYThe localization of V", gene regions to chromosome 2, on which the K locus is located, and to other chromosomes is described. The V", genes that have been transposed to other chromosomes are called orphons. The finding of two new V", genes on chromosome 22 is reported. A V", 11 gene of this region and two V", I genes of the Chr 1 and the cos 118 regions were sequenced. The two V", I orphon sequences and two others that had been determined previously were 97.5% identical, indicating that they may have evolved from a common ancestor by amplification. A model of the evolution of the human V", orphons is discussed.
INTRODucnONThe light chains of the K type of the human immunoglobulins are encoded by numerous V", gene segments and by one J ",-C", gene segment. Functional K genes are formed by recombination of one V", gene segment with J ",C", (for reviews, see
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