A polymer containing a repeating peptide sequence can stimulate T-cell-independent IgG antibody production in Vivo

Hillman, Kathleen; Shapira‐Nahor, Orit; Blackburn, Robert J.; Hernandez, Diana; Golding, Hana

doi:10.1016/0008-8749(91)90326-7

Cited by 23 publications

(9 citation statements)

References 25 publications

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“…The detectable level of the neutralizing antibody in C3H/HeN nu/nu mice may explain why no deaths were recorded during the observation period. It has been postulated that viruses can evoke an antibody response in athymic mice in a relatively T cell-independent fashion (Hillman et al, 1991). A normal level of neutralizing antibody, presumably IgM, was exhibited in mice depleted of T Schmidt, 1984).…”

Section: Discussionmentioning

confidence: 93%

Persistence of Replicating Coxsackievirus B3 in the Athymic Murine Heart is Associated with Development of Myocarditic Lesions

Sato

Tsutsumi

Burke

et al. 1994

Journal of General Virology

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Section: Discussionmentioning

confidence: 93%

Persistence of Replicating Coxsackievirus B3 in the Athymic Murine Heart is Associated with Development of Myocarditic Lesions

Sato

Tsutsumi

Burke

et al. 1994

Journal of General Virology

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“…However, detection of a limited T-cell repertoire in nude mice (7,23), including helper T cells specific for the TI antigen flagellin (23), indicated a role for T cells in the immune response to TI antigens. In addition, T cells specific for another TI antigen, a carbohydrate of group C streptococci, were established from peripheral blood lymphocytes of rabbits hyperimmunized with group C vaccines (24).…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, we previously showed that the ordered polymer (ProGly-Pro), was TI, whereas the random polymer of identical amino acid composition, (Pro66,Gly34),, was TD (6). Similarly, Hillman et al (7) demonstrated that the polymerized form of a human CD4 peptide (amino acids 303-315) could elicit humoral immune response in nude mice, in contrast to the unmodified free peptide (7). However, this requirement is insufficient for thymus independence, since several synthetic multichain polypeptides with repeating antigenic determinants are, nevertheless, TD (8), including (Tyr-Tyr-Glu-Glu)-MATERIALS AND METHODS Mice.…”

mentioning

confidence: 99%

Ia-antigen-T-cell interactions for a thymus-independent antigen composed of D amino acids.

Zisman¹,

Dayan²,

Sela³

et al. 1993

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

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Synthetic polypeptide antigens of L amino acids, although bearing repeating sequences, are thymusdependent (L-TD), whereas the same polymers composed of D amino acids are thymus-independent (D-TI), probably due to a slower rate of metabolism. Yet we found that lymph-node cells of BALB/c mice immunized with D-TI proliferate in response to it in vitro. To follow T-cell activation by D-TI, we established T-cell hybridomas to D-TI and to its analog composed of L isomers, L-TD, for comparison. The T-cell hybridomas express membrane a/fl T-cell receptors and secrete interleukin 2 upon stimulation with the respective antigen. In addition, D-TIspecific hybridomas are stimulated, to a lesser extent, by the L-TD antigen, whereas only some L-TD-specific hybridomas recognize D-TI. Moreover, biotinylated analogs of D-TI and L-TD bind to splenic antigen-presenting cells (APCs) from BALB/c mice. Binding is inhibited by an excess of nonbiotinylated L-TD, and by an excess of a peptide comprising residues 259-271 of the human acetylcholine receptor a subunit, which binds to I-Ad and I-Ed molecules without prior processing. Analysis of APC lysates following incubation of the APCs with biotinylated D-TI and L-TD reveals that the biotinylated antigen moiety is associated with Ia molecules. D-TI and L-TD bind to Ia molecules on intact APCs with similar KD values, 5 x 10-8 M and 3 x 10-8 M, respectively. However, D-TI has faster kinetics of binding than L-TD, probably due to different processing requirements. Hence, we have demonstrated a major histocompatibility complex class Il-mediated T-cell response to a thymus-independent antigen. poly(DLAla)--poly(Lys) [a poly(Lys) backbone with Tyr-TyrGlu-Glu-poly(DLAla) side chains] (9).Another important feature of TI antigens is a slow rate of metabolism (10, 11), which results in persistence of detectable amounts of antigens in macrophages of the spleen and lymph nodes several weeks after immunization (10,12). Thus, (Tyr-Glu-Tyr-Glu)-poly(DLAla)--poly(Lys), which is slowly metabolized by macrophages, is TI, whereas the analog with the faster clearance, (Tyr-Tyr-Glu-Glu)-poly(DLAla)--poly(Lys), is TD (13). Similarly, a branched polypeptide that is built of L amino acids, poly(Phe,Glu)-poly(Pro)--poly(Lys), is TD (L-TD), whereas its analog that is composed of D isomers of the same amino acids, poly-(DPhe,DGlu)-poly(DPro)--poly(DLys), is TI (D-TI), probably due to its slow degradation.Subsequently it was shown that extensive depletion of T cells from splenic lymphocyte populations significantly reduced the in vitro B-cell responses to TI antigens. The latter responses required, in addition to T cells, Ia-bearing adherent cells (14).In this paper we describe the establishment and characterization of T-cell hybridomas specific to the TI branched polypeptide D-TI, in comparison to T-cell hybridomas specific to L-TD, a polypeptide that has the same amino acid composition but of L isomers. In addition, we show that D-TI is presented to T cells by Ia molecules on antigen-presenting cells (AP...

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“…Polyclonal B-cell activators exert their effects through different pathways. Thus, natural or synthetic B-cell mitogens, LPS, or antibodies directed to surface immunoglobulin, directly induce the proliferation of B cells, regardless of their antigen specificity [10][11][12][13]. LPS, for instance, a classical T-cell-independent B-cell mitogen, stimulates naive B cells in the absence of T-cell help.…”

Section: Introductionmentioning

confidence: 99%

A Trypanosoma cruzi Alkaline Antigen Induces Polyclonal B‐Cell Activation of Normal Murine Spleen Cells by T‐Cell‐Independent, BCR‐Directed Stimulation

Zúñiga

Minóprio

et al. 1999

Scand J Immunol

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A Trypanosoma cruzi Alkaline Antigen Induces Polyclonal B-Cell Activation of Normal Murine Spleen Cells by T-Cell-Independent, BCR-Directed Stimulation. Montes CL, Zuñiga E, Minoprio P, Vottero-Cima E, Gruppi A. Scand J Immunol 1999;50:159-166 We have previously reported that a cytosolic alkaline fraction (FI) obtained from epimastigotes of Trypanosoma cruzi promotes the activation, proliferation and differentiation of normal murine B cells into antibody-secreting plasmocytes. Neither the mechanism nor the cells involved in the FI-induced polyclonal B-cell activation were established. In this work we report that accessory cells are required for FI-induced polyclonal B-cell activation as no proliferative responses were obtained following treatment of normal spleen mononuclear cells (NSMC) with L-leucine methyl ester. Furthermore, FI did not induce the expression of CD25 on T cells and it promoted the proliferation of a T-cell-depleted population, indicating that it acts in a T-independent manner. We observed that NSMC were stimulated in vitro by FI-released cytokines, such as interleukin (IL)-4, IL-6 and IL-10, which are involved in B-cell proliferation and differentiation. Interestingly, while significant amounts of interferon-␥ (IFN-␥) were found in culture supernatants we did not observe detectable levels of IL-2. Additionally, we found that B-cell receptor (BCR) and major histocompatibility complex (MHC) class II antigens were involved in the proliferative response induced by FI because antibodies directed against cell-surface immunoglobulin M (IgM), CD45 and MHC class II molecules inhibited the FIinduced B-cell proliferation. CD40 ligand (CD40L) did not participate in such a phenomenon.

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A polymer containing a repeating peptide sequence can stimulate T-cell-independent IgG antibody production in Vivo

Cited by 23 publications

References 25 publications

Persistence of Replicating Coxsackievirus B3 in the Athymic Murine Heart is Associated with Development of Myocarditic Lesions

Persistence of Replicating Coxsackievirus B3 in the Athymic Murine Heart is Associated with Development of Myocarditic Lesions

Ia-antigen-T-cell interactions for a thymus-independent antigen composed of D amino acids.

A Trypanosoma cruzi Alkaline Antigen Induces Polyclonal B‐Cell Activation of Normal Murine Spleen Cells by T‐Cell‐Independent, BCR‐Directed Stimulation

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