The semiotics of charge

Nm, Green

doi:10.1038/351349a0

Cited by 20 publications

(8 citation statements)

References 16 publications

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“…Furthermore, previous studies using clonotypic anti-Ti and anti-CD3e mAb have suggested a 1 : 1 ratio for anti-Ti and anti-CD3e mAb [21,22]. Based on these observations aTcR model containing two Ti dimers, one CD3ye dimer, one CD36e dimer, and one CD3sI; dimer has been suggested [7,8]. By studyingT cells with four functional Ti chains (Tiu, P, y, and S), dimers containing combinations of chains other than Tiup and Tiy6 could not be detected [23, 241 and we have recently shown that TiaP and Tiy6 dimers were expressed in separate TcR complexes in such cells [13].…”

Section: Discussionmentioning

confidence: 89%

Structure of the T cell receptor in a TiαVβ2,αVβ8‐positive T cell line

Hou¹,

Dietrich²,

Kuhlmann

et al. 1994

Eur J Immunol

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The T cell receptor (TcR) is composed of at least six different polypeptide chains consisting of the clonotypic Ti heterodimer (Ti alpha beta or Ti gamma delta) and the noncovalently associated CD3 chains (CD3 gamma delta epsilon zeta). The exact number of subunits constituting the TcR is still not known; however, it has been suggested that each TcR contains two Ti dimers. To gain insight into the structure of the TcR we constructed a Ti alpha V beta 2, alpha V beta 8-positive T cell line which expressed the endogenous human TiV beta 8 and the transfected mouse TiV beta 2 both in association with the endogenous Ti alpha and CD3 chains at the cell surface. Preclearing experiments with radioiodinated cell lysate prepared with digitonin lysis buffer demonstrated that depleting the lysate of Ti alpha V beta 8 by immunoprecipitation with anti V beta 8 monoclonal antibody (mAb) did not reduce the amount of Ti alpha V beta 2 in the lysate, and likewise, depleting the lysate of Ti alpha V beta with anti-V beta 2 mAb did not reduce the amount of Ti alpha V beta 8. Comodulation experiments showed that V beta 8 and V beta 2 did not comodulate with each other. Furthermore, functional tests demonstrated that TcR containing V beta 8 and TcR containing V beta 2 mediated transmembrane activation signals independently of each other. These data demonstrate that mouse V beta 2 and human V beta 8 were not expressed in the same TcR in agreement with a TcR model where each TcR contains only one Ti dimer.

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Section: Discussionmentioning

confidence: 89%

Structure of the T cell receptor in a TiαVβ2,αVβ8‐positive T cell line

Hou¹,

Dietrich²,

Kuhlmann

et al. 1994

Eur J Immunol

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“…It could be placed in the symmetry axis, near the two C ␤ transmembrane regions, bridging the two hemireceptors (44). The two positive-charged transmembrane residues either in each TCR␣ chain or in the TCR␤-TCR␤ pair thus may be buried by the two negative charges present in each neighbor-parallel transduction module (11). Coreceptors are proposed to dock to the TCR͞CD3 complex in an oriented fashion and only after the TCR engages the antigen͞MHC ligand (6,45).…”

Section: Resultsmentioning

confidence: 99%

“…On the one hand, several groups have suggested that TCR, like Ig, is multivalent, [i.e., (␣␤) 2 TCR and (HϩL) 2 Ig]. It was argued that such an arrangement: i) maximizes the interactions between charged transmembrane residues in ␣␤TCR (3 ϩ ) and CD3͞ (6 Ϫ ) chains, rendering a more stable complex, and ii) fits with the hydrodynamic measurements of TCR͞CD3 complex size (11)(12)(13). On the other hand, recent biochemical analyses argue against a multivalent TCR model because immunoprecipitations with mAb to V ␣ or V ␤ failed to reveal the predicted association of two TCR␣s or two TCR␤s in lysates of T cells bearing two distinct ␣␤TCRs (14,15).…”

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confidence: 99%

Multivalent structure of an αβT cell receptor

Fernández-Miguel

Alarcón²,

Iglesias³

et al. 1999

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

122

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Whether there is one or multiple ␣␤T cell antigen receptor (TCR) recognition modules in a given TCR͞ CD3 complex is a long-standing controversy in immunology. We show that T cells from transgenic mice that coexpress comparable amounts of two distinct TCR␤ chains incorporate at least two ␣␤TCRs in a single TCR͞CD3 complex. Evidence for bispecific ␣␤TCRs was obtained by immunoprecipitation and immunoblotting and confirmed on the surface of living cells both by f luorescence resonance energy transfer and comodulation assays by using antibodies specific for TCR␤-variable regions. Such (␣␤) 2 TCR͞CD3 or higher-order complexes were evident in T cells studied either ex vivo or after expansion in vitro. T cell activation is thought by many, but not all, to require TCR cross-linking by its antigen͞major histocompatibility complex ligand. The implications of a multivalent (␣␤) 2 TCR͞CD3 complex stoichiometry for the ordered docking of specific antigen͞major histocompatibility complex, CD4, or CD8 coreceptors and additional TCRs are discussed.The T cell receptor complex (TCR͞CD3) consists of disulfidelinked ␣␤ heterodimers noncovalently associated with invariant proteins of the CD3 (CD3␥, ␦, and ) and the (, , and FcRI␥) families (1-3). The TCR␣ and TCR␤ components contain variable (V) and constant (C) domains homologous to those of antibodies (Ig), but they are not secreted and recognize antigen fragments embedded in molecules of the major histocompatibility complex (MHC) (4-6). The CD3͞ subunits have both signaling and structural functions (7,8). Whether one or multiple ␣␤TCR heterodimers occur in a TCR͞CD3 complex currently is unresolved. A reassessment of TCR stoichiometry began after the finding that two CD3 chains occur per TCR͞CD3 complex (9, 10), because early studies indicated a 1:1 ratio for TCR͞CD3 chains using mAbs to TCR and CD3 for estimation of the number of binding sites (1). On the one hand, several groups have suggested that TCR, like Ig, is multivalent, [i.e., (␣␤) 2 TCR and (HϩL) 2 Ig]. It was argued that such an arrangement: i) maximizes the interactions between charged transmembrane residues in ␣␤TCR (3 ϩ ) and CD3͞ (6 Ϫ ) chains, rendering a more stable complex, and ii) fits with the hydrodynamic measurements of TCR͞CD3 complex size (11-13). On the other hand, recent biochemical analyses argue against a multivalent TCR model because immunoprecipitations with mAb to V ␣ or V ␤ failed to reveal the predicted association of two TCR␣s or two TCR␤s in lysates of T cells bearing two distinct ␣␤TCRs (14, 15).Previous studies of the TCR͞CD3 subunit stoichiometry (9, 10, 15) have relied on the ability to coprecipitate from surface-labeled cells two homologous forms of a given subunit that were distinguishable after gel electrophoresis and autoradiography. Although such an experimental design allowed to show that two CD3 subunits, of human and mouse origin, occur per TCR͞CD3 complex (9, 10), it may be not of universal application. We and others have noticed that the similarity between two distinct TCR␣...

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“…It should be noted that the exaet number of modules existing per TCR is unknown. The present estimate is based on the assumption that the TCR/GD3 complex is made 01 lour dimers: all, y&, oe, and " (Koning et al, 1990; but see Manolios et al , 1991;Green, 1991;and Finkel et al, 1991 tor other poss/ble subunil eombinations). Further work mayaiso break the yöe "unif into two lunetional modules made of y& and öe.…”

Section: Discussionmentioning

confidence: 99%

The T cell receptor/CD3 complex is composed of at least two autonomous transduction modules

Wegener

Letourneur

Hoeveler

et al. 1992

Cell

415

294

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SummaryReeent studies have demonstrated that the CD3-~ subunlt of the T eell antigen reeeptor (TCR) eomplex Is involved In signal transduetlon. However, the funetlon of the remalnlng Invariant subunits, CD3-y, -ö, and e, Is still poorly understood. To examine thelr role In TCR funetlon, we have eonstrueted TCR/CD3 eomplexes devold of tunetlonal ~ subunlt and showed that they are still able to trigger the produellon of Interleukln-2 in response to antigen or superantigen. These data, together with previous results, Indleate that the TCR/ CD3 eomplex Is eomposed of at least two parallel Iransduelng unlts, made 01 the YÖE and ~ ehalns, respeetlvely, Furthermore, the analysis 01 partially truneated ~ ehains has led us to Indlvlduallze a lunetlonal domaln that may have eonstltuted the buildlng block of most of the transduelng subunlts assoelated wlth antigen reeeptors and some Fe receptors. IntroduetionThe T cell antigen receptor (TCR) is a multisubunit complex composed of the products of at least six distinct genes. The TCR a and TCR ß subunits exist as disulfidelinked heterodimers, possess short cytoplasmic tails, and contain clonally variable regions that determine the antigenic specificity of the complex. The remaining subunits, termed CD3-y, -ö, -E, -~, and -1], are invariant, noncovalently associated with the TCR aß dimer, and possess large intracytoplasmic domains thought to be responsible for coupling antigen recognition to various signal transductlon pathways. The evolutionarily related y, Ö, and e subunits are expressed as noncovalently associated ye and OE pairs (Koning et al., 1990;Blumberg et al. , 1990; De la Herra et al. , 1991), and display immunoglobulin-like extracellular domains (Gold et al., 1987). In contrast, the ~ and 1] subunlts contaln an extracellular domain of only 9 residues and constitute the prototype of a new protein family that includes the y chain of the high affinity IgE receptor (FceRI)

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The semiotics of charge

Cited by 20 publications

References 16 publications

Structure of the T cell receptor in a TiαVβ2,αVβ8‐positive T cell line

Structure of the T cell receptor in a TiαVβ2,αVβ8‐positive T cell line

Multivalent structure of an αβT cell receptor

The T cell receptor/CD3 complex is composed of at least two autonomous transduction modules

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