Predominant use of a particular α-chain in suppressor T cell hybridomas specific for keyhole limpet hemocyanin

Koseki, Haruhiko; Imai, Kenji; Ichikawa, Tomohiko; Hayata, Isamu; Taniguchi, Masaru

doi:10.1093/intimm/1.6.557

Cited by 54 publications

(34 citation statements)

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“…2b). As KLH-Ts hybridomas all use this a chain (13), it is likely that the self ligand cross-reacts with the nominal antigen KLH. The amino acid in the VJjunctional region is always a glycine (Fig.…”

Section: Results and Discussion Predominant Expression Of The V14+ Tcmentioning

confidence: 99%

“…Other strains, including B10 congenic lines used, were also maintained by K.M. A thymoma cell line of AKR origin, BW5147, and a keyhole limpet hemocyanin (KLH)-specific suppressor T-cell (Ts) hybridoma (BW5147 x C57BL/6 Ts; 34S-281) used in the present studies have been described (12,13 Bone Marrow Chimeras. Bone marrow chimeras were prepared as described (17).…”

Section: Methodsmentioning

confidence: 99%

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Homogenous junctional sequence of the V14+ T-cell antigen receptor alpha chain expanded in unprimed mice.

Koseki

Imai

Nakayama

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

108

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Nucleotide sequences of VJ (variable-joining) junctional regions of V14' a-chain T-cell receptor genes show that most VaW4+ T cells use one a chain (Val4Ja281 with a one-nucleotide N region, which is frequently used in keyhole limpet hemocyanin-specific suppressor T-celi hybridomas) in unprimed mice. Moreover, the frequency of this a-chain expression was >1.5% of the total a chains found in laboratory strains, including B10 congenic mice. This is about 104 times higher than was expected. The V14J281 a-chain expression was relatively low but was significant in CD41/CD81 immature thymocytes and became quite high in mature single-positive T cells, implying that this a chain is selected during T-cell maturation. V14J281 expression increased with time after birth and reached a maximum at around 5 weeks of age. The ligand seems to be a self molecule and to be present in laboratory strains but to be absent in a wild mouse, Mus musculus molossinus, because bone marrow chimeras clearly showed that bone marrow cells derived from Mus musculus molossinus negative for this a chain raised V14J281-positive T cells in a C57BL/6 environment. The above results suggest that there are some selection mechanisms for this cell type other than those for conventional afi T cells and also that the homogenous VJ junction of the V14J281 a chain plays a pivotal role in the selection of the T cell and its ligand reactivity.Thymus-derived lymphocytes (T cells) recognize antigens in the context of the polymorphic parts of major histocompatibility complex (MHC) class I or class II molecules by virtue ofthe heterodimeric a/3 T-cell receptor (TCR), which is found on the vast majority of mature T cells in the thymus and peripheral lymphoid tissues (1, 2). A second TCR, y8 TCR, has also been identified (3, 4) and found to be relatively abundant in some adult mouse organs and among fetal thymocytes.The T-cell repertoire seems to be generated by two selection mechanisms during T-cell We provide evidence herein that some T cells use a homogenous a chain (V14J281). This seems to be a consequence of selection and expansion ofthis T-cell type, because its frequency is >1.5% of the total a chains in the peripheral lymphoid organs. Moreover, studies using bone marrow chimeras suggest that the ligand is an unidentified self molecule. The results indicate that the homogenous VJjunctional region of the V14J281 a chain, in particular, plays a crucial role in the selection of this type of T cell and its ligand reactivity. MATERIALS AND METHODSAnimals and Cell Lines. Pathogen-free C57BL/6 mice were purchased from Shizuoka Experimental Animal Co., Hamamatsu, Japan. A wild Japanese mouse strain, Mus musculus molossinus, was established and maintained by K.M. Other strains, including B10 congenic lines used, were also maintained by K.M. A thymoma cell line of AKR origin, BW5147, and a keyhole limpet hemocyanin (KLH)-specific suppressor T-cell (Ts) hybridoma (BW5147 x C57BL/6 Ts; 34S-281) used in the present studies have been described (12,13

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Section: Results and Discussion Predominant Expression Of The V14+ Tcmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Homogenous junctional sequence of the V14+ T-cell antigen receptor alpha chain expanded in unprimed mice.

Koseki

Imai

Nakayama

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

108

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“…We provide evidence here that the homogeneous Va14-Ja281 is selected according to rules partly distinct from those currently accepted for the selection of TCR repertoire in the thymus (19)(20)(21)(22). (23,24).…”

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confidence: 79%

Dominant expression of a distinctive V14+ T-cell antigen receptor alpha chain in mice.

Koseki

Asano

Inaba

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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A distinctive variable region 14-positive (V14+) a chain (V.14') of the T-cell antigen receptor is predominantly expressed in multiple mouse subspecies. The VJ14 family has two members, Val4.1 and Val4.2, which differ by only three amino acids at positions 50-52. Based on the EcoRI restriction fragment length polymorphism of the gene encoding V.14, mice can be divided into three groups:type I with an 11.2-kilobase (kb) fragment, type II with a 2.0-kb fragment, and type m with the 2.0-kb and 11.2-kb fragments.Usage of V,14-J.281, where J.281 is an a-chain joining segment, with a one-base, N region dominates at the level of 0.02-1.5% of a chains in all laboratory strains, Mus musculus castaneus, and Mus musculus domesticus but not in Mus musculus molossinus, Mus musculus musculus, and Mus spicilegus samples. The preferential Val4Ja281 expression seems to be due to positive selection because the V-Jjunctional region is always glycine, despite the ability of the V.14 gene to associate with J. other than JL281. As Va14-Ja281 expression is independent of known maijor histocompatibility complex antigens, including H-2, TLA, Qa, and HMIT, the selecting ligand must be a monomorphic molecule of the mouse, expressed in a subspecies-specific manner. Additional observations, such as the expression of homogeneous V.14-J.281 in athymic mice, suggest that the positive selection of V.14' T cells occurs extrathymically.

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“…In parallel with the discovery of Vb8-biased DN thymocytes, Taniguchi and colleagues [4,5], who had been working for some time on keyhole limpet hemocyanin-specific suppressor T cell hybridomas, discovered recurrent use of an unusual TCRa chain with an invariant Va14-Ja18 rearrangement. Using this Va14i chain as a probe in elegant RNAse protection experiments they subsequently made the remarkable discovery that this TCRa chain was utilized by a significant proportion of peripheral T cells (estimated at 1-2%) in lymphoid tissues of most strains of normal mice [10].…”

Section: The Invariant Va14 Chainmentioning

confidence: 99%

“…A third report followed shortly thereafter [3]. Around the same time an unusual invariant TCR Va14-Ja18 rearrangement was cloned from a panel of keyhole limpet hemocyaninspecific suppressor T cell hybridomas [4,5]. Collectively these studies provided the first glimpse of what are now known as invariant natural killer T (iNKT) cells, but the road to that conclusion proved to be unusually long and winding.…”

Section: Introductionmentioning

confidence: 99%

NKT cells: In the beginning…

MacDonald

2007

Eur. J. Immunol.

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Invariant natural killer T (iNKT) cells as we know them today are a unique subset of mature T cells co-expressing a semi-invariant Va14/Vb8 TCR and surface markers characteristic of NK cells. The semi-invariant TCR on iNKT cells recognizes glycolipids bound to monomorphic CD1d molecules, leading to rapid cytokine production. The purpose of this historical perspective is to describe how a series of seemingly unrelated findings in the late 1980s and early 1990s crystallized in the discovery of iNKT cells. The story is told from a personal viewpoint, with a particular effort to place both breakthroughs and misinterpretations in the context of their era. IntroductionIn the summer of 1987 two groups independently reported the identification of a mysterious subset of CD4 -CD8 -(double-negative, DN) thymocytes that overexpress the TCR Vb8 gene segment [1,2]. A third report followed shortly thereafter [3]. Around the same time an unusual invariant TCR Va14-Ja18 rearrangement was cloned from a panel of keyhole limpet hemocyaninspecific suppressor T cell hybridomas [4,5]. Collectively these studies provided the first glimpse of what are now known as invariant natural killer T (iNKT) cells, but the road to that conclusion proved to be unusually long and winding. The purpose of this "historical" feature is to recount this process of discovery from a personal viewpoint, highlighting both breakthroughs and misinterpretations along the way. Vb8-biased DN thymocytesGiven that most iNKT cells express CD4 and are preferentially localized in the liver, it may seem surprising that they were first identified as a DN subset in the thymus. However, two independent sets of circumstances contributed to this discovery. First a number of groups, including our own, were actively dissecting thymus subsets in the mid 1980s using flow cytometry and a growing battery of monoclonal antibodies (mAb). It became clear from the work of Fowlkes and Mathieson [6] that the very small DN subset (2-3% of thymocytes) contained immature precursors capable of differentiating into all other thymus subsets. This finding prompted intense scrutiny of the DN population by most groups working on T cell development.The second key catalyst to the discovery of iNKT cells was the successful production of the first allotypic mAb to the TCR by the Kappler/Marrack [7] and Bevan [8] groups. Although the TCRb and TCRa chains had been molecularly cloned, by this time no mAb to Vb domains had been identified. By pure serendipity these mAb were both directed against the Vb8 domain that is dramatically over-represented among iNKT cells. Thus it rapidly became clear that the DN thymocyte subset had a TCR repertoire that was heavily biased towards Vb8 [1][2][3].With hindsight it is interesting to note that this first glimpse of iNKT cells was interpreted incorrectly by both groups that made the initial discovery. Based on the dogma that DN thymocytes were immature, we speculated that the Vb8-biased subset might arise from preferential usage of certain Vb domains early in deve...

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Predominant use of a particular α-chain in suppressor T cell hybridomas specific for keyhole limpet hemocyanin

Cited by 54 publications

References 0 publications

Homogenous junctional sequence of the V14+ T-cell antigen receptor alpha chain expanded in unprimed mice.

Homogenous junctional sequence of the V14+ T-cell antigen receptor alpha chain expanded in unprimed mice.

Dominant expression of a distinctive V14+ T-cell antigen receptor alpha chain in mice.

NKT cells: In the beginning…

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