Claire Langlet

Centre d'Immunologie de Marseille-Luminy, Marsiglia, Provence-Alpes-Côte d'Azur, France

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Publications (18)133.12 Total impact

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    ABSTRACT: Data presented in this publication are aimed at defining the role of the Ti/CD3, Thy-1, and Ly-6 structures of mouse CTL clones for two measurable activation-dependent effector functions: target-cell killing and production of g-interferon (g-IFN). The killing function is not dependent on protein synthesis and can be measured within minutes of CTL-target-cell interaction, as recently shown using digital imaging of changes in intracytoplasmic Ca++ concentration ([Ca++]i) in effector and target cells loaded with the Ca++ sensitive dye Fura-2. g-IFN synthesis is dependent on transcriptional activation and is optimally measured in supernatants around 20 h after CTL-target-cell interaction or after binding of anti-Ti mAb.
    Annals of the New York Academy of Sciences 12/2006; 532(1):33 - 43. DOI:10.1111/j.1749-6632.1988.tb36323.x · 4.31 Impact Factor
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    ABSTRACT: C2GnT-I [core2 beta(1,6)-N-acetyglucosaminyltransferase-I] and FucT-VII [alpha(1,3)-fucosyltransferase-VII] are the key enzymes for the biosynthesis of sialyl-Lewis x determinants on selectin ligands and therefore they represent good drug targets for the treatment of inflammatory disorders and other pathologies involving selectins. In the present study, we examined the importance of N-glycosylation for the ability of C2GnT-I and FucT-VII to generate functional selectin ligands, particularly the PSGL-1 (P-selectin glycoprotein ligand-1). We found that (i) both enzymes have their two N-glycosylation sites occupied, (ii) for C2GnT-I, the N-glycan chain linked to Asn-95 significantly contributes to the synthesis of functional PSGL-1 and is required to localize the enzyme to the cis/medial-Golgi compartment, (iii) all N-glycosylation-deficient proteins of FucT-VII displayr a dramatic impairment of their in vitro enzymatic activities, but retain their ability to fucosylate the core2-modified PSGL-I and to generate P- and L-selectin binding, and (iv) the glycomutants of FucT-VII fail to synthesize sialyl-Lewis x or to generate E-selectin binding unless core2-modified PSGL-1 is present. All combined, our results show a differential functional impact of N-glycosylation on C2GnT-1 and FucT-VII and disclose that a strongly reduced FucT-VII activity retains the ability to fucosylate PSGL-1 on the core2-based binding site(s) for the three selectins.
    Biochemical Journal 12/2005; 391(Pt 3):491-502. DOI:10.1042/BJ20050344 · 4.78 Impact Factor
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    ABSTRACT: The integral membrane adaptor protein linker for activation of T cells (LAT) couples the T-cell receptor (TCR) with downstream signalling and is essential for T-cell development and activation. Here, we investigate the dynamic distribution of LAT-GFP fusion proteins by time-lapse video imaging of live T lymphocytes interacting with antigen-presenting cells. We show that LAT forms two distinct cellular pools, one at the plasma membrane and one that co-distributes with transferrin-labelled intracellular compartments also containing the TCR/CD3-associated zeta chain. The distribution of LAT between these two pools is dependent on LAT intracytoplasmic residues. Whereas plasma membrane-associated LAT is recruited to immune synapses after a few seconds of cell conjugate formation, the intracellular pool is first polarized and then recruited after a few minutes. We further show that LAT intracytoplasmic amino acid residues, particularly the Tyr136, 175, 195 and 235 residues, are required for its own recruitment to the immune synapse and that a herein-identified juxtamembrane LAT region (amino acids 32-104) is involved in the localization of LAT in intracellular pools and in T-cell signalling. Altogether, our results demonstrate that LAT controls its own recruitment at the immune synapse, where it is required as a scaffold protein for the signalling machinery. The results also suggest that the intracellular pool of LAT might be required for T-cell activation.
    Journal of Cell Science 04/2004; 117(Pt 7):1009-16. DOI:10.1242/jcs.00968 · 5.33 Impact Factor
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    ABSTRACT: During inflammation, E- and P-selectins appear on activated endothelial cells to interact with leukocytes through sialyl-Lewis x and sialyl-Lewis a antigens (sLe(x/a)). These selectins can also interact with tumor cells in a sialyl-Lewis-dependent manner and for this reason, they are thought to play a key role in metastasis. Diverting the biosynthesis of sialyl-Lewis antigens toward nonadhesive structures is an attractive gene therapy for preventing the hematogenous metastatic spread of cancers. We have previously shown that transfection of alpha(1,2)-fucosyltransferase-I (FUT1) in Chinese hamster ovary (CHO) cells had a slight effect on the overall sialylation while the synthesis of sLE(x) was dramatically prevented. We herein delivered the gene of FUT1 by a human immunodeficiency virus-derived lentiviral vector to three human cancer cell lines including pancreatic (BxPC3), hepatic (HepG2), and colonic (HT-29) cancer cells. We found that on FUT1 transduction, all cells exhibited a dramatic decrease in sLe(x) synthesis with a concomitant increase in Le(y) and Le(b) expression, without any detectable effect on the level of cell surface sLe(a) antigens. In parallel, FUT1-transduced HT-29 and HepG2 cells, but not BxPC3 cells, failed to interact with E-selectin as assessed by E-selectin-binding assay or dynamic adhesion to activated endothelial cells. We show also that transduced FUT1 efficiently fucosylates the P-selectin ligand PSGL-1 without altering P-selectin binding. These results have important implications for understanding cell-specific reactions underlying the synthesis of selectin ligands in cancer cells and may provide a basis for the development of anti-metastatic gene therapy.
    American Journal Of Pathology 03/2004; 164(2):371-83. DOI:10.1016/S0002-9440(10)63127-6 · 4.60 Impact Factor
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    ABSTRACT: Recent studies suggest that rafts are involved in numerous cell functions, including membrane traffic and signaling. Here we demonstrate, using a polyoxyethylene ether Brij 98, that detergent-insoluble microdomains possessing the expected biochemical characteristics of rafts are present in the cell membrane at 37 degrees C. After extraction, these microdomains are visualized as membrane vesicles with a mean diameter of approximately 70 nm. These findings provide further evidence for the existence of rafts under physiological conditions and are the basis of a new isolation method allowing more accurate analyses of raft structure. We found that main components of T cell receptor (TCR) signal initiation machinery, i.e. TCR-CD3 complex, Lck and ZAP-70 kinases, and CD4 co-receptor are constitutively partitioned into a subset of rafts. Functional studies in both intact cells and isolated rafts showed that upon ligation, TCR initiates the signaling in this specialized raft subset. Our data thus strongly indicate an important role of rafts in organizing TCR early signaling pathways within small membrane microdomains, both prior to and following receptor engagement, for efficient TCR signal initiation upon stimulation.
    The EMBO Journal 05/2002; 21(8):1899-908. DOI:10.1093/emboj/21.8.1899 · 10.75 Impact Factor
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    ABSTRACT: Antigen-independent adhesive interactions between T lymphocytes and antigen-presenting cells (APCs) are essential for scanning for specific antigens on the APC surface and for initiating the immune response. Here we show, through time-lapse imaging of live cells, that the intercellular adhesion molecule 3 (ICAM-3, also known as CD50) is clustered specifically at the region of the T lymphocyte surface that initiates contact with APCs. We describe the role of ICAM-3 in T cell-APC conjugate formation before antigen recognition, in early intracellular signaling and in cytoskeletal rearrangement. Our data indicate that ICAM-3 is important in the initial scanning of the APC surface by T cells and, therefore, in generating the immune response.
    Nature Immunology 03/2002; 3(2):159-68. DOI:10.1038/ni753 · 24.97 Impact Factor
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    ABSTRACT: The beta 1,6 N-acetylglucosaminyltransferase (C2GnT) has been recently mapped to the cis/medial-Golgi compartment. To analyze the Golgi-targeting determinants of C2GnT, we constructed various deletion mutants of the enzyme fused to the enhanced green fluorescent protein (EGFP) and localized these proteins by fluorescence microscopy in living cells. We found that the N-terminal peptide encompassing amino acids 1 to 32 represents the minimal Golgi-targeting signal sufficient to localize EGFP to the same compartment as the full-length C2GnT. This peptide makes up the cytoplasmic and the transmembrane domains of the enzyme and was referred to as CTd (cytoplasmic and transmembrane domains). We compared the Golgi-targeting efficiency of the C2GnT-derived CTd with its homologous domains from other glycosyltransferases, including the H-type alpha(1,2)-fucosyltransferase (FucTI), the polypeptide N-acetylgalactosaminyltransferase-I (GalNAcT-I), the alpha(1,3)-fucosyltransferase VII (FucTVII), and the alpha(2,6)-sialyltransferase (ST6Gal-I) and found that the Golgi-targeting determinants of these glycosyltransferases were also composed of their cytosolic and transmembrane domains. To investigate whether the CTd of C2GnT could serve as a cis to medial Golgi-specific signal, we tested its ability to mislocalize two late-Golgi acting glycosyltransferases FucTI and FucTVII. We show that fusing the C2GnT-derived CTd with the catalytic domain of FucTVII resulted in a complete mislocalization of the enzyme to the C2GnT compartment, with a parallel alteration of sialyl-Lewis x synthesis and P-selectin binding. The intracellular distribution and activity of FucTI, however, were not affected. Thus, CTds of either early or late-Golgi acting glycosyltransferases represent the Golgi-targeting domains of these enzymes. In addition, we show that C2GnT-derived CTd can function as a cis/medial Golgi-targeting determinant.
    Glycobiology 02/2002; 12(1):15-24. · 3.14 Impact Factor
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    ABSTRACT: The recent recognition of the presence of rafts in the plasma membrane and of their involvement in cell signaling has strongly stimulated the search for their function in receptor-mediated signal transduction in lymphocytes. Recent progress suggests that a general feature of membrane rafts is to serve as platforms wherein the signaling cascades triggered through different multichain immune recognition receptors (e.g. the TCR, BCR and FcϵRI) are initiated and organized.
    Current Opinion in Immunology 07/2000; 12(3-12):250-255. DOI:10.1016/S0952-7915(00)00084-4 · 7.87 Impact Factor
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    ABSTRACT: T-cell receptors (TCRs) upon binding to peptide-MHC ligands transduce signals in T lymphocytes. Tyrosine phosphorylations in the cytoplasmic domains of the CD3 (gammadeltaepsilon) and zeta subunits of the TCR complex by Src family kinases initiate the signaling cascades via docking and activation of ZAP-70 kinase and other signaling components. We examined the role of the low-density detergent-insoluble membranes (DIMs) in TCR signaling. Using mouse thymocytes as a model, we characterized the structural organization of DIMs in detail. We then demonstrated that TCR engagement triggered an immediate increase in the amount of TCR/CD3 present in DIMs, which directly involves the engaged receptor complexes. TCR/CD3 recruitment is accompanied by the accumulation of a series of prominent tyrosine-phosphorylated substrates and by an increase of the Lck activity in DIMs. Upon TCR stimulation, the DIM-associated receptor complexes are highly enriched in the hyperphosphorylated p23 zeta chains, contain most of the TCR/CD3-associated, phosphorylation-activated ZAP-70 kinases and seem to integrate into higher order, multiple tyrosine-phosphorylated substrate-containing protein complexes. The TCR/CD3 recruitment was found to depend on the activity of Src family kinases. We thus provide the first demonstration of recuitment of TCR/CD3 to DIMs upon receptor stimulation and propose it as a mechanism whereby TCR engagement is coupled to downstream signaling cascades.
    The EMBO Journal 10/1998; 17(18):5334-48. DOI:10.1093/emboj/17.18.5334 · 10.75 Impact Factor
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    ABSTRACT: Although much has been learned about CD8 structure-function properties, it has so far not been tested whether the nature of the TCR is sufficient to transfer the property of CD8 dependence versus non-dependence to CD8+ cytotoxic T lymphocytes (CTL) and their precursors differentiating in T cell receptor (TCR)-transgenic (Tg) mice. In the present study, we compared the characteristics of dependence on CD8 for stimulation of CTL precursors and antigen-specific cytolysis by CD8+ T cells from two TCR-Tg mice expressing respectively the TCR (Tg) from a "CD8-dependent" and from a "CD8-independent" CTL clone, which were both reactive against the H-2Kb alloantigen and originated from H-2k mice. The results indicate that the property of the Tg+CD8+ cells from H-2k TCR-Tg mice corresponds to that of the CTL clone of origin, demonstrating that it is linked to the nature of the TCR. Consistent with this property, Tg+CD4+ cells could also differentiate into H-2Kb-specific CTL when originating from the "CD8-independent", but not from the "CD8-dependent" Tg-TCR. The influence of the property of "CD8 dependence" on negative selection occurring in TCR-Tg H-2k/b mice was apparent at two levels: (i) in the thymus, the extent of deletion was much more pronounced for the "CD8-independent" TCR-Tg mice; (ii) in the periphery, Tg+(hi) cells with low to negative CD8 expression were present for the "CD8-dependent" Tg-TCR, whereas only Tg+CD4-CD8- cells with low surface Tg-TCR and CD3 expression were found for the "CD8-independent" Tg-TCR, indicating that Tg+CD4-CD8- cells are susceptible to tolerance induction involving TCR/CD3 surface down-modulation. Furthermore, different in vitro conditions led to H-2Kb-induced stimulation of Tg+CD4-CD8- cells to differentiate into CTL detected in an anti-TCR clonotypic monoclonal antibody redirected cytolysis assay. Culture in interleukin-2 of H-2k/b Tg+CD4-CD8- cells was sufficient to induced CTL activity in the "CD8-independent" model, whereas stimulation with cells which overexpressed H-2Kb was required in addition to interleukin-2 to induce CTL differentiation in the "CD8-dependent" model. These data suggest that peripheral Tg+CD4-CD8- cells present in a situation of in vivo tolerance to H-2Kb can still be triggered by H-2Kb with a sensitivity correlated with the degree of CD8 dependence.
    European Journal of Immunology 07/1994; 24(7):1572-7. DOI:10.1002/eji.1830240718 · 4.52 Impact Factor
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    ABSTRACT: We have studied tolerance induction in transgenic CBA mice expressing H-2Kb genes under the influence of guinea-pig alpha-lactalbumin (KAL) or human beta-globin gene promoter (K beta). KAL radio-resistant cells, but not bone marrow derived cells, induce tolerance to H-2Kb in chimeric mice. In contrast, bone marrow derived and radio-resistant cells of K beta mice induce tolerance. Although appropriate, tissue-specific, expression of H-2Kb molecules occurs in KAL and K beta mice, H-2Kb is expressed at low levels in thymus of transgenic mice. In addition, dendritic cells and macrophages express H-2Kb molecules when K beta, but not when KAL bone marrow is cultured in vitro. The mode of tolerance induction was examined in double transgenic mice by mating KAL or K beta mice to mice expressing TCR transgenes (Tg-TCR) derived from a H-2Kb specific, CD8-independent cytotoxic T cell clone. In both cases, a large number of Tg-TCR+ CD8+CD4+ thymocytes develop but mature CD8+CD4- thymocytes fail to appear suggesting that thymocytes are eliminated late in development. Some CD8-CD4- and CD8-CD4+ Tg-TCR+ T cells develop in double transgenic mice and respond to activation through their TCR-CD3 complex in vitro, although no responses to stimulation with H-2Kb expressing cells were detected. Thus, tolerance induction in KAL and K beta mice proceeds via a deletional mechanism that is inefficient due either to low numbers of H-2Kb expressing thymic cells or to the low levels of H-2Kb expressed by thymic cells, or to a combination of these factors.
    International Immunology 03/1994; 6(2):277-87. · 3.18 Impact Factor
  • Claire Langlet · A M Schmitt-Verhulst
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    ABSTRACT: Signal transduction mechanisms leading to effector functions in mouse cytolytic T lymphocyte (CTL) clones were studied following the introduction of exogenous molecules by electroporation. Conditions were defined in which the application of an electric pulse permeabilized the CTL without affecting functions such as antigen-dependent or antibody-mediated cytotoxicity. When a non-permeant Ca2+ chelator such as EGTA was added in the external medium during the electric pulse, it inhibited subsequent target cell cytolysis carried out in the presence of external Ca2+, thereby indicating the efficiency of EGTA uptake. Results obtained in this system, using a 13 amino-acid protein kinase C (PKC) pseudo-substrate peptide, indicated that it selectively inhibited cytolysis, whereas a substrate peptide with one amino-acid substitution was not inhibitory. This suggests that the technique could be used to study the signal transduction mechanisms of CTL clones which lead to the expression of effector functions.
    Journal of Immunological Methods 08/1992; 151(1-2):107-15. DOI:10.1016/0022-1759(92)90108-6 · 2.01 Impact Factor
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    ABSTRACT: In this study, we demonstrated that some V beta 6+, CD4+, Mls-1a-specific T cell clones had cytolytic activity when stimulated with anti-T cell receptor(TcR)/CD3 monoclonal antibodies (mAb), but not with targets expressing Mls-1a, although they produced lymphokines (interleukin 2 and interferon-gamma) in response to both types of stimuli. To examine the possibility that lack of cytolysis resulted from expression of the Mls-1a antigen on merely a fraction of splenic B blasts, we (a) used the B cell lymphoma LBB.3.4.16 and (b) measured esterase secretion which is generally concurrent with cytotoxic T lymphocyte (CTL) activity. The B cell lymphoma maximally stimulated the T cell clone for interferon-gamma production when responding and stimulating cells were incubated at a 1:1 ratio, but it was never killed by the Mls-1a-specific T cell clone unless TcR/CD3-specific mAb were added. Furthermore, a fivefold excess of the Mls-1a B cell lymphoma did not induce any secretion of esterase, which was observed only in the presence of the TcR/CD3-specific mAb. Comparison of the reactivity of two Mls-1a-specific T cell hybridomas expressing the same TcR at similar surface density, revealed both quantitative and qualitative differences between CD3-specific mAb and Mls stimulation of the hybridomas. A small quantitative difference in the sensitivity of hybridoma FJ22.5 to stimulation with V beta 6 or CD3-specific mAb resulted in a marked decrease in efficiency of stimulation by Mls-1a for interleukin 2 production and to inability to detect growth inhibition by Mls-expressing cells. A qualitative difference was observed when analyses of inositol phosphate production were performed under optimal conditions of stimulation of the highly responsive T cell hybridoma (FJ8.1): only stimulation with CD3-specific mAb, but not Mls-expressing cells, could induce detectable inositol phosphate production. Lack of cytolysis of Mls-1a class II-expressing B cells may have evolutionary significance in view of the recent mapping of Mls to mouse mammary tumor virus genes.
    European Journal of Immunology 10/1991; 21(10):2581-2589. DOI:10.1002/eji.1830211040 · 4.52 Impact Factor
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    ABSTRACT: This chapter highlights positive and negative liposome-based immunoselection techniques. Liposomes are vesicles composed of one or several phospholipid bilayers surrounding a closed aqueous compartment. They are useful for marking, killing, or rescuing cell populations. The use of liposomes as fluorescent reagents, notably for the cell sorter, offers high signal with low background. Liposomes are formed with the compound of interest encapsulated within the enclosed space or as part of the component phospholipids. After liposome formation, the liposomes are coupled to the freshly activated protein at room temperature, usually by mixing the protein and liposomes and dialyzing against buffered saline at pH 8–8.5 for several hours. High specificity of action is the case for the use of liposomes for negative selection, which requires that the target determinant is endocytosed by the cell, in contrast to the action of antibody and complement, for which expression of the molecule in question is sufficient for the cell to be killed. Positive selection with liposome-encapsulated protective reagents, though studied in a small number of model systems, is seriously challenged only by the fluorescence-activated cell sorter, which has been used for this application in only a few laboratories highly experienced in its use.
    Methods in cell biology 02/1989; 32:447-71. DOI:10.1016/S0091-679X(08)61185-1 · 1.44 Impact Factor
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    ABSTRACT: The T cell receptor alpha and beta chain genes donated by an H-2 class I-specific, CD8-dependent cytotoxic T cell clone were transferred, alone or in combination with the Lyt-2 gene, into a class II-restricted, CD4+ T cell hybridoma. Two important points emerged. First, the alpha and beta T cell receptor genes endowed the recipient with the H-2 class I specificity of the donor only if the same cell had also been transfected with the Lyt-2 gene. Second, the functional Lyt-2 molecule was expressed on the transfected cells in the absence of the Lyt-3 polypeptide. These results demonstrate that, besides the T cell receptor, the Lyt-2 polypeptide is the only subset-specific molecule required to retarget a class II-reactive, CD4+ T cell line toward H-2 class I molecules.
    Cell 09/1987; 50(4):545-54. DOI:10.1016/0092-8674(87)90027-4 · 33.12 Impact Factor
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    ABSTRACT: The activation-induced phosphorylation of T-cell antigen receptor (Ti)-associated proteins was investigated in order to analyse possible signal-transduction mechanisms leading to two distinct effector functions of a mouse cytolytic T-cell clone (KB5.C20): target cell killing (independent of protein synthesis) and de novo production of gamma interferon (gIFN; dependent on gIFN gene expression). Ti-associated T3-like proteins were first identified by immunoprecipitation of 125I-labelled cell surface proteins from 1% digitonin lysates of clone KB5.C20 by 1- and 2-dimensional (non-reduced (NR)/reduced (R)) gel electrophoresis. In addition to the alpha and beta chains of the Ti (NR: 80-Kd; R: 43 and 40 Kd), two doublets of 35-37 Kd (NR) and 32-34 Kd (NR) leading to bands of 25, 16 and 14 Kd (R) were identified, as well as three bands (25, 23 and 22 Kd (NR)) leading to 27-, 25- and 21-Kd bands (R). Activation of clone KB5.C20 (prelabelled with 32P-orthophosphate) with either anti-Ti mAb or exposure to both ionomycin and phorbol myristic acetate (PMA) induced the phosphorylation of 21- and 25-27-Kd (R) Ti-associated proteins, whereas exposure to either ionomycin or PMA alone induced only weak phosphorylation of 21-Kd (R) components. A weak phosphorylation of 32- and 34-Kd Ti-associated proteins was sometimes observed after stimulation with anti-Ti mAb. Functional studies suggested that activation for gIFN production was observed only when both the 21- and 25-27-Kd proteins were phosphorylated, whereas activation for killing (when measured by PMA-induced non-specific killing) could occur in conditions where no phosphorylation of the 25-27-Kd protein was detected.
    Annales de l Institut Pasteur Immunologie 01/1987; 138(1):65-82. DOI:10.1016/S0769-2625(87)80097-1
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    ABSTRACT: The present studies have made use of in vitro derived H-2Kb mutants to analyze the fine specificity of alloreactive cytotoxic T lymphocytes (CTL). The variants were derived by negatively selecting mutagenized tumor cells with a monoclonal anti-H-2Kb antibody and positively selecting for residual cells expressing serologically altered H-2Kb molecules. Details of this procedure are described in the companion paper. Selected populations of bulk alloreactive and cloned CTL were examined for recognition of the variants. In contrast to the serologic findings presented in the companion paper, there does not appear to be a correlation between the monoclonal antibody used to select the R8 variant and the CTL specificities recognized. In several instances, CTL clones could discriminate between variants having identical serologic profiles. Therefore, it would appear that the CTL have a large repertoire of allorecognition, even when generated across a mutant anti-Kb combination reflecting only a few amino acid differences. In addition, a diverse set of epitopes can be recognized on the Kb molecule. Finally, in some instances a change in what would appear to be a single amino acid resulted in a profound alteration of CTL recognition even though the Kb mutant molecule expressed limited serologic changes. These results support the idea that small changes in the H-2Kb molecule can have dramatic effects on CTL even though there are relatively little effects on serologic recognition of the target molecule.
    The Journal of Immunology 09/1986; 137(4):1244-50. · 5.36 Impact Factor
  • C Hua · C Langlet · M Buferne · A M Schmitt-Verhulst
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    ABSTRACT: In preparation for functional analyses, a study of the binding of H-2Kb-specific monoclonal antibodies (mAb) to formaldehyde (FOR)-fixed H-2b spleen or tumor cells revealed that three of nine mAb tested had lost reactivity with the FOR-fixed cells, whereas the reactivity of the other mAb generally did not diminish. Comparison of the reactivity of these mAb on untreated H-2Kbm mutant cells and on FOR-treated H-2Kb cells suggests that for three mAb the total loss of reactivity on the latter could be a consequence of the alteration by FOR of lysine 89, which is substituted by alanine in mutant bm3. H-2Kb-specific alloreactive polyclonal or monoclonal CTL, all of which had retained reactivity with bm3 target cells, had also retained reactivity with FOR-fixed H-2b cells as indicated by cold target inhibition studies. The H-2Kb-specific CTL were probably reactive with "conformational" determinants of H-2Kb, which are dependent on the integrity of both the alpha 1 and the alpha 2 domains of the H-2Kb molecule. Results are compatible with FOR treatment selectively affecting a serological determinant in the alpha 1 domain without affecting conformational-type CTL determinants.
    Immunogenetics 02/1985; 21(3):227-34. DOI:10.1007/BF00375375 · 2.49 Impact Factor