Showing papers by "Susumu Tonegawa published in 1986"
TL;DR: The identification of additional Tγ V-gene segments are described and it is demonstrated that they can be rearranged to previously identified J- and C- gene segments and are expressed in fetal thymocytes.
Abstract: The search for the genes encoding the T-cell receptor alpha and chains revealed a third gene, T gamma (ref. 1), which shares with t T alpha (refs 2-7) and T beta (refs 8-15) genes a number of structure features, including somatic rearrangement during T-cell development. T gamma gene expression appears to be unnecessary in son mature T cells and is at its greatest in fetal thymocytes encouraging speculation that T gamma has a role in T-cell development and may be involved in the recognition of polymorphic major histocompatibility complex (MHC) products during thymic education. One argument against the participation of T gamma in such a process has been its apparently limited diversity, due to the small number of gene segments available for rearrangement. We here describe the identification of additional T gamma V-gene segments and demonstrate that they can be rearranged to previously identified J- and C-gene segments and are expressed in fetal thymocytes. In addition we describe a variety of patterns of T gamma mRNA processing which may be significant for T gamma gene regulation.
388 citations
TL;DR: It appears that the binding sites of the antigen-specific T-cell alpha beta-chain receptors and of antibodies are very similar in their overall dimensions and geometry: a T- cell alpha beta receptor molecule probably has an antigen- specific binding site that is fundamentally no different than the conventional binding site of an antibody.
Abstract: To explore the possibility that the difference in antigen recognition between B and T cells derives from a structural difference in their respective antigen-specific receptors (immunoglobulins on B cells and immunoglobulin-like molecules on T cells), we compared the extracellular segments of the T-cell receptor alpha, beta, and gamma polypeptide chains and the N-terminal segment of the T-cell T8 (Lyt-2) antigen chain with the corresponding regions of immunoglobulins whose three-dimensional structures are known The results indicate that the four T-cell polypeptide chains are organized into immunoglobulin-like domains consisting of multistranded antiparallel beta-sheet bilayers Invariant amino acid side chains that are conserved in diverse immunoglobulins, including those that mediate domain-domain interactions and form a constant scaffold for antibody binding sites, are also conserved in the chains encoded by the T-cell receptor genes and in the N-terminal domain of T8 (Lyt-2) It appears that the binding sites of the antigen-specific T-cell alpha beta-chain receptors and of antibodies are very similar in their overall dimensions and geometry: a T-cell alpha beta receptor molecule probably has an antigen-specific binding site that is fundamentally no different than the conventional binding site of an antibody
140 citations
TL;DR: The pattern of γ-gene rearrangements in these cell lines indicate that a polypeptide product of the previously reported γ gene, V2J2–C2, is not expressed in them and is, therefore, not necessary for the antigen-specific cytotoxic and proliferative responses of these mature T cells.
Abstract: Structural similarities between surface immunoglobulins (s Ig) on B cells and antigen-specific receptors on T cells suggest that a T cell, like a B cell, should express only two immunoglobulin-like genes, one for each subunit of the disulphide-linked, heterodimeric, antigen-specific (alpha beta) T-cell receptor. However, cytotoxic T lymphocytes (Tc cells) and immature thymocytes also contain RNA transcripts of a third immunoglobulin-like gene, called gamma (refs 1-4). A polypeptide corresponding to the gamma gene has not yet been identified and the function of this gene remains an enigma. Judging from its nucleotide sequence, the rearranged gamma gene is expected to encode an integral membrane polypeptide chain, and gamma complementary DNAs from two cloned Tc cell lines have previously been found to have different sequences around the V-J (variable region-joining region) junction, suggesting that, in these cells, the gamma-gene product is a clonally diverse surface structure that may form part of an as yet unidentified, antigen-specific receptor. To analyse further the extent of diversity of the gamma-gene product, we have determined the partial sequences of 11 gamma cDNA clones from three other cloned Tc cell lines, and report here that the sequences are indeed clonally diverse, but in all instances they are out-of-phase in the region of the V-J junction. This finding and the pattern of gamma-gene rearrangements in these cell lines indicate that a polypeptide product of the previously reported gamma gene, V2J2-C2, is not expressed in them and is, therefore, not necessary for the antigen-specific cytotoxic and proliferative responses of these mature T cells.
60 citations
TL;DR: A cytotoxic-T-cell-associated phosphorylated protein, many of whose properties suggest that it may be the product of the T-cell gamma gene, is described, which is greatly enhanced by interleukin 2 stimulation.
Abstract: The previously determined sequence of the murine T-cell gamma gene and its transcription in cloned T lymphocytes suggests that the polypeptide encoded by this gene is generally present in cytotoxic T cells as a 33-kDa monomer in a disulfide-bonded dimer. The gamma chain is also expected to be phosphorylated because a sequence in its cytoplasmic domain is homologous to an active site for serine phosphorylation in the regulatory subunit of cAMP-dependent protein kinase. We describe here a cytotoxic-T-cell-associated phosphorylated protein, many of whose properties suggest that it may be the product of the T-cell gamma gene. Its phosphorylation is greatly enhanced by interleukin 2 stimulation.
2 citations
Patent•
20 Oct 1986
1 citations