Contrasting contributions of complementarity-determining region 2 and hypervariable region 4 of rat BV8S2+ (V 8.2) TCR to the recognition of myelin basic protein and different types of bacterial superantigens

Kreiß, Matthias; Asmuss, A; Krejci, Kathrin; Lindemann, Dirk; Miyoshi‐Akiyama, Tohru; Uchiyama, Takehiko; Rink, Lothar; Broeren, Chris P. M.; Herrmann, Thomas

doi:10.1093/intimm/dxh068

Cited by 18 publications

(37 citation statements)

References 55 publications

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Section: Cellsmentioning

confidence: 99%

“…28 58C-CD28 ϩ are ␣␤ TCR Ϫ 58C mouse T hybridoma cells transduced for rat/mouse CD28 expression. 29,30 53/4-CD28 cells are 53/4 cells (a sister clone of the rat/mouse T-cell hybridoma 35/2), which express a rat ␣␤ TCR recognizing a guinea pig MBP 68-88 peptide restricted to RT1B I (rat MHC class II) and are also transduced for rat/mouse CD28 expression. 29 The 2A␥␦ TCR MOP is a 2A peptide-linked V␥9V␦2 TCR cloned into either pczCFG5IEGN-or pczCFG5IH MuLV-based retroviral expression vectors 31 and transduced into either 58C-CD28 ϩ or in 53/4-CD28 ϩ T-cell hybridomas.…”

Section: Cellsmentioning

confidence: 99%

“…Stimulation of 2A␥␦ TCR MOP ϩ 58C-CD28 or 2A␥␦ TCR MOP ϩ 53/4-CD28 murine hybridoma cells was performed similarly as previously described. 30,31 …”

mentioning

confidence: 99%

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Key implication of CD277/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human γδ T-cell subset

Harly

Guillaume

Nédellec

et al. 2012

Blood

471

632

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Introduction␥␦ T cells are key players in the immune surveillance of cellular distress, thanks to their ability to recognize conserved determinants up-regulated after inflammation, infection, or cell transformation. 1,2 Although ␥␦ T-cell receptors (TCRs) contribute to detection of danger-associated determinants, ligands for these receptors have been identified in a few cases only. 3 Thus, the antigenic specificity of ␥␦ T cells and their fine activation modalities in response to cell stress remain largely unknown.One of the best studied ␥␦ T-cell subsets in humans expresses V␥9V␦2 TCR and predominates in blood, composing several percent of the whole peripheral lymphoid pool in most adults. V␥9V␦2 T cells are activated by nonpeptidic phosphorylated isoprenoid pathway metabolites, 4-6 hereafter referred to as phosphoagonists (PAg). Natural V␥9V␦2-stimulating PAg include isopentenyl pyrophosphate (IPP), 7 a metabolite of the mevalonate pathway found in mammalian cells and the desoxyxylulose phosphate pathway shared by many microorganisms, and hydroxy-methyl-butyl-pyrophosphate, 8 an intermediate of the latter pathway. PAg detection by ␥␦ T cells underlies their broad reactivity toward infected and transformed cells. Indeed, tumor cell recognition by V␥9V␦2 T cells is linked to enhanced production of the weak agonist IPP, resulting from increased cell metabolism and cholesterol biosynthesis. Accordingly, pharmacologic inhibitors of the mevalonate pathway that up-regulate (eg, aminobisphosphonates, NBP) or down-regulate (eg, statins) IPP production, respectively, increase or decrease antitumor V␥9V␦2 T-cell responses. 9,10 Moreover, because of the high V␥9V␦2 T cell-stimulating activity of the microbial agonist hydroxy-methyl-butyl-pyrophosphate, V␥9V␦2 T-cell responses are elicited by infected cells producing even traces of this PAg. 8 Although PAg-induced activation is restricted to V␥9V␦2 T cells and can be conferred by V␥9V␦2 TCR gene transfer, 11,12 attempts to detect cognate interactions between PAg and V␥9V␦2 TCR have failed so far. 13 So how V␥9V␦2 T cells sense PAg remains an enigma. PAg rapidly induce Ca 2ϩ signaling and activation of V␥9V␦2 T-cell clones, but this requires cell-to-cell contact, suggesting the implication of additional target cell surface receptors in this phenomenon. 11,14 PAg elicit V␥9V␦2 T-cell responses against basically all human cells, irrespective of their tissue origin, but do not induce recognition of any murine target cells. Therefore, the putative target cell receptors involved in PAg-mediated T-cell activation are expected to be broadly expressed by human, but not murine, cells.Activation of antigen-stimulated T cells is tuned by interactions involving T cell-derived CD28-related receptors and target cellderived B7-related counter-receptors, 15 which family includes members, such as Skint and butyrophilin (BTN) receptors. The mandatory role played by Skint-1 in the intrathymic positive There is an Inside Blood commentary on this article in this issue.The online version of this...

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Section: Cellsmentioning

confidence: 99%

Section: Cellsmentioning

confidence: 99%

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Key implication of CD277/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human γδ T-cell subset

Harly

Guillaume

Nédellec

et al. 2012

Blood

471

632

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“…Cloning of rat AV14S6 (nomenclature as proposed in [22], previously called rat AV14S1 [20]) and mouse AV14S1A2 α chains as well as rat BV8S4-like (CDR2+4), rat BV8S2 CDR3β #1, and mouse BV8S2 β chains has been described in [34] and [15], respectively. Cloning of rat AV14S2 α chain has been described in [29].…”

Section: Cloning and Expression Of Primary Rat And Mouse Inkt Tcrmentioning

confidence: 99%

The hypervariable region 4 (HV4) and position 93 of the α chain modulate CD1d‐glycolipid binding of iNKT TCRs

et al. 2015

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TCRs of invariant NKT (iNKT) cells bind α-galactosylceramide (αGC) loaded CD1d in a highly conserved fashion and show a characteristic TCR gene usage: An "invariant" α chain with a canonical AV14/AJ18 rearrangement in mice (AV24/AJ18 in humans) is paired with β chains containing characteristic Vβ segments. In the rat, a multimember AV14 gene family increases the variability within this system. This study characterizes CD1d binding of rat AV14 gene segments in TCR transductants as well as CD1d binding and iNKT TCR expression of expanded polyclonal F344 rat iNKT populations. It defines an important role of position 93 at the V-J transition for TCR avidity and species cross-reactivity of the rat iNKT TCR. Furthermore, for the first time we identified variability within the fourth hypervariable loop (HV4) of the α chain as a modulator of CD1d:αGC binding in rat and mouse. Additionally, we confirmed the importance of the CDR2β for CD1d:αGC binding, but also show that the CDR3β may even have opposite effects on binding depending on the pairing α chain. Altogether, we characterized naturally occurring sources of variability for the iNKT TCR and speculate that they rather level than increase the largely germline encoded differences of iNKT TCR ligand avidity.Keywords: CD1d r iNKT cells r Molecular modeling r Rat r T-cell receptors Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionType 1 NKT cells (invariant NKT (iNKT) cells) are a subset of αβ T cells characterized by the expression of a semi-invariant TCR. In contrast to conventional αβ T cells, iNKT cells are not MHCrestricted, but recognize CD1d, a nonpolymorphic MHC class Ilike molecule presenting lipid antigens [1,2]. The lineage-defining iNKT TCR contains an invariant α chain with a uniform AV14/AJ18 rearrangement in mice (AV24/AJ18 in human) and a limited number of β chain V segments (mostly BV8S2, BV7, and BV2 in mice Correspondence: Prof. Thomas Herrmann e-mail: herrmann-t@vim.uni-wuerzburg.de and the BV8S2 homologue BV11 in humans) [3][4][5][6][7]. This decreased variability within the TCR leads to a very restricted CDR repertoire with CDR3β as the only exception.The first characterized and one of the strongest antigens for iNKT cells is KRN7000 (α-galactosylceramide, αGC), the synthetic derivative of a compound isolated from the marine sponge Agelas mauritanus [3]. The rather fixed mode of interaction between the iNKT TCR and the CD1d:αGC complex does not only allow for direct identification of iNKT cells by CD1d oligomers loaded with αGC or its derivative PBS57, but also defines this lineage of αβ T cells. Crystallographic studies have shown that, for mouse and human, direct contact is mostly mediated by CDR1α, CDR3α, and CDR2β of the iNKT TCR, displaying the restricted usage of CDRs within this system [8,9]. Thereby, an alanine C 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2015. 45: 2122-2133 Molecular immunology 2123 scanning mutagenesis study...

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“…The resulting fragment, which encoded the leader and the first 72 aa of mature V region peptide, was coligated with a EspI-F344/Crl cDNA-BamHI fragment (encoding the JC terminus of another liver-derived ␣-chain) into the EcoRI/BamHI sites of pczCGZ5 IEGN vector, and the insert was sequenced. The generation of the rat BV8S2 ␤-chain and its mutants has been described elsewhere (33).…”

Section: Cloning and Expression Of Rat And Mouse Inkt Tcrmentioning

confidence: 99%

The Complementarity Determining Region 2 of BV8S2 (Vβ8.2) Contributes to Antigen Recognition by Rat Invariant NKT Cell TCR

Pyż

Naidenko

Miyake

et al. 2006

The Journal of Immunology

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Invariant NKT cells (iNKT cells) are characterized by a semi-invariant TCR comprising an invariant α-chain paired with β-chains with limited BV gene usage which are specific for complexes of CD1d and glycolipid Ags like α-galactosylceramide (α-GalCer). iNKT cells can be visualized with α-GalCer-loaded CD1d tetramers, and the binding of mouse CD1d tetramers to mouse as well as to human iNKT cells suggests a high degree of conservation in recognition of glycolipid Ags between species. Surprisingly, mouse CD1d tetramers failed to stain a discrete cell population among F344/Crl rat liver lymphocytes, although comprised iNKT cells are indicated by IL-4 and IFN-γ secretion after α-GalCer stimulation. The arising hypothesis that rat iNKT TCR recognizes α-GalCer only if presented by syngeneic CD1d was then tested with the help of newly generated rat and mouse iNKT TCR-transduced cell lines. Cells expressing mouse iNKT TCR reacted to α-GalCer presented by rat or mouse CD1d and efficiently bound α-GalCer-loaded mouse CD1d tetramers. In contrast, cells expressing rat iNKT TCR responded only to α-GalCer presented by syngeneic CD1d and bound mouse CD1d tetramers only poorly or not at all. Finally, CD1d-dependent α-GalCer reactivity and binding of mouse CD1d tetramers was tested for cells expressing iNKT TCR comprising either rat or mouse AV14 (Vα14) α-chains and wild-type or mutated BV8S2 (Vβ8.2) β-chains. The results confirmed the need of syngeneic CD1d as restriction element for rat iNKT TCR and identified the CDR2 of BV8S2 as an essential site for ligand recognition by iNKT TCR.

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Contrasting contributions of complementarity-determining region 2 and hypervariable region 4 of rat BV8S2+ (V 8.2) TCR to the recognition of myelin basic protein and different types of bacterial superantigens

Cited by 18 publications

References 55 publications

Key implication of CD277/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human γδ T-cell subset

Key implication of CD277/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human γδ T-cell subset

The hypervariable region 4 (HV4) and position 93 of the α chain modulate CD1d‐glycolipid binding of iNKT TCRs

The Complementarity Determining Region 2 of BV8S2 (Vβ8.2) Contributes to Antigen Recognition by Rat Invariant NKT Cell TCR

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