Acquisition of cytotoxic T lymphocyte-specific carbohydrate differentiation antigens.

Lefrançois, Leo; Puddington, Lynn; Machamer, Carolyn E.; Bevan, Michael J.

doi:10.1084/jem.162.4.1275

Cited by 62 publications

(34 citation statements)

References 67 publications

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“…20 Our data indicate that the p240 and p220 epitopes were originally hidden by sialic acid, whereas this was an integral part of the Ag structure of the low MW isoforms. 25 Activation of T cells results in the loss of sialic acid on membrane glycoproteins. Sialic acid might thus be targeted in the y isoforms by certain autoAb.…”

Section: Discussionmentioning

confidence: 99%

CD45 autoantibodies mediate neutralization of activated T cells from lupus patients through anergy or apoptosis

Mamoune¹,

Kerdreux²,

Durand³

et al. 2000

Lupus

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The objectives were to provide estimates of the prevalence of autoantibody (Ab) directed to CD45 in lupus patients, identify the target autoantigen(s), and determine the ability of such reactivity to mediate neutralization of T lymphocytes. Sera from 64 patients were studied using 2 assays: Western blot and an ELISA with CD45 eluted from 3 cell lines as antigen (U937, Jurkat and Daudi). The role of carbohydrate specificity was investigated using enzyme digestion of blotted glycans, competition with sugars, and inhibition with lectins. Apoptosis was studied through annexin V binding, and cell cycle analysis using the propidium iodide method. AutoAb to CD45 were detected in 16/64 sera (25%) by Western blot, and 21/32 sera (66%) found positive in the ELISA. CD45 purified from Daudi cells was identified in the ELISA, but not in the blot. AutoAb were of the IgM and the IgG isotypes, but not specific for a particular cell type or CD45 isoform: 2 dominant specificities were recognized, one against p180, and another against high MW isoforms. Neuraminidase-induced enhancement of reactivity, together with the inhibitory effect of N-acetyl galactosamine and Dolichos diflorus lectin suggest that the epitopes are carbohydrates. AutoAb which were specific for activated CD4+T cells triggered the annexin V binding, and, in 2 of 4 cases, lymphocytes underwent apoptosis. In conclusion, carbohydrate conformational epitopes may be important as target antigens, and some CD45 autoAb have the capacity to neutralize activated T cells through anergy or apoptosis.

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Section: Discussionmentioning

confidence: 99%

CD45 autoantibodies mediate neutralization of activated T cells from lupus patients through anergy or apoptosis

Mamoune¹,

Kerdreux²,

Durand³

et al. 2000

Lupus

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“…Similarly, stimulation of murine cytotoxic T lymphocytes leads to greatly increased expression of specific activation antigens defined by monoclonal antibodies designated CT1 and CT2 [Lefrancois and Bevan, 1985a, b]. CT1 and CT2 are directed against the Sd a antigen attached to a core 2 O-glycan backbone [Lefrancois et al, 1985;Lefrancois and Kanagawa, 1986;Conzelmann and Lefrancois, 1988]. An identical sequence was identified in the murine ZP during our recent studies [Easton et al, 2000].…”

Section: Evidence For the Existence Of The Srsmentioning

confidence: 97%

The Species Recognition System: A New Corollary for the Human Fetoembryonic Defense System Hypothesis

Clark

Dell²,

Morris³

et al. 2000

Cells Tissues Organs

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We have previously suggested that the human fetus is protected during human development by a system of both soluble and cell surface associated glycoconjugates that utilize their carbohydrate sequences as functional groups to enable them to evoke tolerance. The proposed model has been referred to as the human fetoembryonic defense system hypothesis (hu-FEDS). In this paradigm, it has previously been proposed that similar oligosaccharides are used to mediate crucial recognition events required during both human sperm-egg binding and immune-inflammatory cell interactions. This vertical integration suggested to us that the sperm-egg binding itself is related to universal recognition events that occur between immune and inflammatory cells, except that in this case recognition of ‘species’ rather than recognition of ‘self’ is being manifested. In this paper, we have designated this component of hu-FEDS as the species recognition system (SRS). We propose that the SRS is an integral component of the hu-FEDS used to enable sperm-egg recognition and protection of the gametes from potential immune responses. Recent structural data indicates that the glycan sequences implicated in mediating murine gamete recognition are also expressed on CD45 in activated murine T lymphocytes and cytotoxic T lymphocytes. This overlap supports our contention that there is an overlap between the immune and gamete recognition systems. Therefore the hu-FEDS paradigm may be a subset of a larger model that also applies to other placental mammals. We therefore propose that the hu-FEDS model for protection should in the future be referred to as the eutherian fetoembryonic defense system hypothesis (eu-FEDS) to account for this extension. The possibility exists that the SRS component of eu-FEDS could predate eutherians and extend to all sexually reproducing organisms. Future investigation of the interactions between the immune and gamete recognition system will be required to determine the degree of overlap.

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“…Thymocytes were fixed with 3% (wt/vol) paraformaldehyde in PBS, washed, and treated with or without 0.08 M sodium m-periodate in 0.05 M sodium acetate buffer, pH 5 .5, at 37°C for 2 h, as described elsewhere (32,33) .…”

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confidence: 99%

Natural autoantibodies to thymocytes: origin, VH genes, fine specificities, and the role of Thy-1 glycoprotein.

Hayakawa

Carmack

Hyman

et al. 1990

The Journal of Experimental Medicine

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Summary15 SM/J mouse hybridoma antibodies that show antithymocyte autoantibody (ATA) activity by immunofluorescence staining were studied. Half of these antibodies react with determinants whose expression is associated with Thy-1, as shown by blocking experiments with antiThy-1 and loss of reactivity with Thy-1 -mutant cell lines . The Thy-1 dependence of three of these ATA is further confirmed by their reexpression on a Thy-1 gene transfectant . However, the remaining antibodies exhibited binding that showed little or no dependence on Thy-1. Furthermore, we find that most ATA derives from the Ly-1 B subpopulation, as demonstrated by lipopolisaccharideinduced ATA secretion in vitro and by comparison of ATA hybridoma frequencies. V region gene sequence data of 14 monoclonal ATA from Ly-1 B cell-derived hybridomas reveal the utilization of nine V genes belonging to four different V H families (J558, 3609, Q52, and Vgam3.8) . While we find that two of these hybridomas arose from a clonal expansion, we also find four examples of a 3609 family V gene utilized in clonally independent lines showing similar specificity. Yet another example of identical V gene usage by clonally unrelated cells is found in two J558 ATA of a distinct fine specificity. These data suggest that the enrichment of ATA B cells in the Ly-1 B subset is primarily due to repeated independent recruitment of B cells by antigen resulting in the expression of a restricted set of VH genes.

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Acquisition of cytotoxic T lymphocyte-specific carbohydrate differentiation antigens.

Cited by 62 publications

References 67 publications

CD45 autoantibodies mediate neutralization of activated T cells from lupus patients through anergy or apoptosis

CD45 autoantibodies mediate neutralization of activated T cells from lupus patients through anergy or apoptosis

The Species Recognition System: A New Corollary for the Human Fetoembryonic Defense System Hypothesis

Natural autoantibodies to thymocytes: origin, VH genes, fine specificities, and the role of Thy-1 glycoprotein.

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