A polymorphism of the rat T-cell receptor β-chain variable gene 13 ( BV13S1 ) correlates with the frequency of BV13S1-positive CD4 cells

Stienekemeier, Martina; Hofmann, Kathrin; Gold, Ralf; Herrmann, Thomas

doi:10.1007/s002510050623

Cited by 11 publications

(31 citation statements)

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“…45: 2122-2133 deficient in iNKT cells [22]. haplotypes, lack a functional BV8S4 and also differ in other BV alleles [19,[30][31][32]. Altogether, we identified for the first time position 68 in the HV4α as modulator of rat and mouse iNKT TCR binding and demonstrate similar effects for position 93 of the α chain as well as for β chain diversity.…”

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confidence: 58%

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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confidence: 58%

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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“…The Tcrb a haplotype, which is found in F344/ Crl and DA rats, expresses BV8S2 and BV8S4, whereas the Tcrb l haplotype of LEW/Cr, BN, and PVG rats expresses only BV8S2 (24,31,41,42). These rat strains are widely used as models for autoimmune diseases; therefore, it is of special interest to investigate whether differences in reactivity to natural iNKT TCR ligands based on differences in the CDR2s of BV8S2 vs BV8S4 could lead to a rat strain-specific variation in iNKT T cell development or Ag reactivity.…”

Section: Discussionmentioning

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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“…Remaining B cells were removed by incubation for 20 min at 4°C on sheep anti-mouse IgG serum (ShaMIg)-coated petri dishes. Thereafter, nonadherent cells were purified by a panning technique as described elsewhere [12,22]. CD8 § g + and CD8 § g -+ˇT cells were obtained by FACS sorting of +ˇT cells isolated as described above.…”

Section: Animals Cell Isolation Purification and Culturementioning

confidence: 99%

Expression of functional CD8α β heterodimer on rat γ δ T cells does not correlate with the CDR3 length of the TCRδ chain predicted for MHC class I-restricted antigen recognition

Sträube

Herrmann

2000

Eur. J. Immunol.

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In accordance with their lack of MHC restriction, most mouse and human γ δ T cells express neither the CD4 nor CD8(α β) coreceptor. In striking contrast, up to 80% of splenic rat γ δ T cells express the CD8α β isoform of CD8, which for the α β T cell subset serves as a marker for MHC class I‐restricted cells. We compared CD8 on α β and γ δ T cells with regard to co‐stimulatory function and correlation of CD8 expression with TCRDV usage and CDR3δ length. In both subsets, CD8 acted as a co‐stimulatory molecule in vitro and was found to bind the kinase lck efficiently. No differences between the CDR3δ length spectra of CD8+ and CD8– γ δ T cells or between unselected thymic and peripheral γ δ T cells were found. As seen in man and mice, CDR3δ were rather long, a structural feature which can be expected to interfere with an α β TCR‐like mode of MHC class I binding. In summary, CD8 expressed by rat γ δ T cells is a molecule with the potential to act as a coreceptor, but its expression gives no indication for antigen recognition analogous to that of MHC class I‐restricted α β T cells.

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A polymorphism of the rat T-cell receptor β-chain variable gene 13 ( BV13S1 ) correlates with the frequency of BV13S1-positive CD4 cells

Cited by 11 publications

References 18 publications

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

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

Expression of functional CD8α β heterodimer on rat γ δ T cells does not correlate with the CDR3 length of the TCRδ chain predicted for MHC class I-restricted antigen recognition

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