Distinct epitopes on the T8 molecule are differentially involved in cytotoxic T cell function

Biddison, William E.; Rao, Patricia E.; Talle, Mary Anne; Boselli, Christine M.; Goldstein, Gideon

doi:10.1016/0198-8859(84)90034-x

Cited by 21 publications

(9 citation statements)

References 26 publications

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“…Therefore, T cells expressing CD4 almost always recognize antigen presented in association with Ia (class II MHC) molecules. This finding has led to the idea that the function of CD4 is to interact specifically with Ia molecules on the APC, thereby strengthening the overall interaction between Ia-restricted T cells and APCs (9)(10)(11)(12). Since no polymorphism for CD4 has been demonstrated, it follows that this molecule would have to recognize a conserved, monomorphic determinant on Ia.…”

mentioning

confidence: 99%

The T-cell accessory molecule CD4 recognizes a monomorphic determinant on isolated Ia.

Buus¹,

Pasternak²,

Kappler³

et al. 1988

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

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The membrane protein CD4 is commonly found on mature T cells specific for antigen in association with class II major histocompatibility complex (MHC; la) proteins. This correlation has led to the suggestion that CD4 binds to a monomorphic region of the Ia molecule on the antigenpresenting cell (APC) and functions either by enhancing interaction between the T cell and the APC, or conversely, by transducing negative signals to the T cell. To address this hypothesis, we have made use of sublines from an unusual T hybrid that is class I MHC restricted but also CD4+. By incorporating purified MHC proteins into a planar membrane system, we show that different Ia molecules can greatly enhance the ability of a CD4+ but not a CD4-variant of this class I-restricted T hybrid to respond to isolated class I molecules. T-cell responses can be strongly augmented by the concurrent expression of CD4 on the T cell and any of four different Ia proteins on planar membranes, thus supporting the idea that CD4 binds to a monomorphic region of the Ia molecule and increases the avidity with which the T cell can interact with its target.

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mentioning

confidence: 99%

The T-cell accessory molecule CD4 recognizes a monomorphic determinant on isolated Ia.

Buus¹,

Pasternak²,

Kappler³

et al. 1988

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

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“…In particular, the CD4 antigen has served as a phenotypic marker for those T lymphocytes that recognize antigen on cells bearing MHC class II molecules (6)(7)(8)(9)(10). Functionally, most of the CD41 lymphocytes in human peripheral blood are helper/inducer cells, although CD4' cytotoxic cells have been detected (1 1).…”

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confidence: 99%

Effect of recombinant soluble CD4 on human peripheral blood lymphocyte responses in vitro.

Liu

1988

J. Clin. Invest.

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We have previously demonstrated that recombinant soluble CD4 protein (rsT4) blocks both HIV-1 infection of CD4 bearing lymphocytes and syncytium formation in vitro. (Recombinant soluble CD4 is designated by rsT4.) Hence, we suggested the use of rsT4 in therapy for AIDS or the prevention of HIV-1 infection in individuals with a known risk of exposure. However, concerns arose that rsT4 might be immunosuppressive because of its implicated role in the enhancement of certain lymphocyte activation events through its engagement of MHC class II molecules on target cells. We therefore assessed the effect of recombinant soluble CD4 upon a number of functional and activation parameters of lymphocytes, including cellular proliferation, IL-2 secretion, and cytolytic capability, after antigenic or mitogenic stimulation. We report here that rsT4, at 60-fold over the concentration needed to block acute HIV-1 infection in vitro, does not significantly inhibit the activation of human peripheral blood lymphocytes by either PHA, tetanus toxoid or allogeneic cells. These results indicate that rsT4 will potentially exert minimal immunosuppressive effects in vivo, thus supporting the feasibility of clinical trials of rsT4 in the treatment or prevention of AIDS. In addition, the implications of these results for the interactions between CD4 and MHC class II molecules during lymphocyte activation are discussed.

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“…Recent studies with monoclonal antibodies have revealed distinct epitopes on human T lymphocyte surface antigens, such as those related to helper (7) and killer/suppressor (2) (5). These antibodies have been useful in detemining the antigenic structure and biological significance of the molecules.…”

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confidence: 99%

New Monoclonal Antibodies That Define Multiple Epitopes and a Human‐Specific Marker on the Interleukin 2 Receptor Molecules of Primates

Tanaka

Inoi

Tozawa

et al. 1986

Microbiology and Immunology

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Twelve hybridoma cell lines producing monoclonal antibodies to the human interleukin 2 (IL-2) receptor (IL-2R) molecule were prepared. These antibodies were characterized by competitive antibody-binding assay and sequential immunoprecipitation assay with four known monoclonal antibodies to the human IL-2R molecule. The twelve new monoclonal antibodies were divided among the four known antibody types, the HIEI-, H-A26-, H-31-, and anti-Tac-type, and an additional new type, the H-48-type. The H-48 antibody did not compete with any other antibodies in the competitive binding assay. The binding of 1-25I-IL-2 to MT-2 cells and the IL-2-dependent growth of normal activated T-cells were both strongly inhibited by all the H-31-and anti-Tac-type antibodies, and partially or slightly inhibited by HIEI-and H-A26-type antibodies, but were not inhibited by the H-48 antibody. Thus, the same type of monoclonal antibodies had a similar effect on the function of IL-2R. These results suggest that epitopes for the same type of antibodies could be single identical epitopes or epitopes closely associated with each other. On the other hand, these antibodies also reacted variously with a panel of various human and simian lymphoid cell lines immortalized with human T-cell leukemia virus type-I (HTLV-I) : the H-45 antibody reacted only with the human cell lines, the H-Cl and H-44 and H-47 antibodies reacted with human and ape cell lines, and the other antibodies reacted with cell lines of humans, apes and Old and New World monkeys. These differences in the reactivity of the antibodies with the primate cell lines suggest that the antigenic structure of the IL-2R molecule changed during evolutionary divergence of the primates.

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Distinct epitopes on the T8 molecule are differentially involved in cytotoxic T cell function

Cited by 21 publications

References 26 publications

The T-cell accessory molecule CD4 recognizes a monomorphic determinant on isolated Ia.

The T-cell accessory molecule CD4 recognizes a monomorphic determinant on isolated Ia.

Effect of recombinant soluble CD4 on human peripheral blood lymphocyte responses in vitro.

New Monoclonal Antibodies That Define Multiple Epitopes and a Human‐Specific Marker on the Interleukin 2 Receptor Molecules of Primates

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