A molecular biology approach to the mechanism of T-cell-mediated cytotoxicity.
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Cloning, Molecular↗
Biomedical subjects
J F Brunet
Publications and source records attributed to J F Brunet.
P815 mastocytoma cells, classical targets for cytotoxic T lymphocytes, exert natural cytotoxicity.
While investigating the tissue distribution of cytotoxic-T-lymphocyte-associated (CTLA) gene transcripts, we found that some of these could be detected in mast cells. This led us to test the cytolysis exerted by a number of mast cell populations. We briefly report here that P815 cells, classically known as excellent target cells for cytotoxic T cells, exert natural cytotoxicity toward WEHI-164 target cells.
Animals↗
The inducible cytotoxic T-lymphocyte-associated gene transcript CTLA-1 sequence and gene localization to mouse chromosome 14.
Classical phenomenological approaches to the study of the mechanism of T-cell-mediated cytotoxicity have now given way to a search for molecules involved in this function; this is attempted either by subcellular and biochemical fractionation of material from cytotoxic cells, or through the characterization of molecules recognized by cytotoxicity-inhibiting monoclonal antibodies Molecules having a role in cytotoxicity may also be identified by detecting the corresponding messenger RNA transcripts. Such an approach may include, as a first step, the search for transcripts as specific as possible to cytotoxic T cells; only secondarily can their actual relevance to cytotoxicity be investigated. We report here the preparation and systematic screening of a differential complementary DNA bank, in which we detected three distinct messenger RNA transcripts (CTLA-1, CTLA-2 and CTLA-3) present in various cytotoxic T cells but not (or less so) in a range of non-cytotoxic lymphoid cells. We describe the co-inducibility of these transcripts and of cytotoxicity in thymocytes and hybridoma cells, the sequence of CTLA-1 cDNA, its protein homology with serine esterases and the localization of the corresponding gene to mouse chromosome 14.
Amino Acid Sequence↗
A new member of the immunoglobulin superfamily--CTLA-4.
The immunoglobulin superfamily is a group of proteins, each made of one or several domains sharing key structural features with either the variable (V) or the constant (C) immunoglobulin domains. It includes such functionally important members as the immunoglobulins themselves, major histocompatibility complex (MHC) class I and class II and T-cell receptor (TCR) molecules. Several members of this superfamily are expressed on lymphocytes where they are membrane-bound and capable of interactions with other members of the family, thus taking part in cell-cell recognition. In screening mouse cytolytic-T-cell-derived cDNA libraries, we came across cDNA clones defining a sequence, CTLA-4, which could encode a 223-amino-acid protein clearly belonging to the immunoglobulin superfamily. It consists of one V-like domain flanked by two hydrophobic regions, one of which has a structure suggestive of membrane anchoring. CTLA-4 is mainly expressed in activated lymphocytes and is coinduced with T-cell-mediated cytotoxicity in inducible models of this process. The mouse ctla-4 gene maps to band C of chromosome 1.
Amino Acid Sequence↗