Long‐term suppressor cell lines. I. Demonstration of suppressive function

Levich, J; Weigle, William O.; Parks, D E

doi:10.1002/eji.1830141202

Cited by 12 publications

(4 citation statements)

References 27 publications

(9 reference statements)

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“…2 Therefore, HEL derivatives used in this study were subjected to assays immediately after purification using cation exchange chromatography. Moreover, it has been demonstrated by Weigle and his colleagues that an aggregated form of human gamma globulin (HGG) is highly antigenic for T-cells (52,53), whereas an aqueous preparation of HGG (deaggregated HGG) that is ultracentrifuged to remove small amounts of aggregates is highly tolerogenic for T-cells, i.e. injection of adult mice with deaggregated HGG renders them immunologically unresponsive to a subsequent injection of the immunogenic HGG (54,55).…”

Section: Discussionmentioning

confidence: 99%

Depression of T-cell Epitope Generation by Stabilizing Hen Lysozyme

So¹,

Ito²,

Koga³

et al. 1997

Journal of Biological Chemistry

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Conformational stability of proteins is an important factor that determines their resistance/susceptibility to proteolytic digestion. Intracellular proteolysis is the key step in antigen presentation events for protein antigens; hence, it is likely that increasing protein stability reduces the antigenicity of proteins. We prepared three hen egg white lysozyme derivatives possessing different stabilities by chemical modification to clarify the relationship between conformational stability and the antigenicity of the protein. One of the derivatives was conformationally unstabilized by removing one intramolecular disulfide bond, whereas the two others were stabilized by the addition of an intramolecular crosslink. The antigenicity of these derivatives was evaluated using hen egg white lysozyme-specific T-cell hybridoma cells and a B-lymphoma cell line, A20, as antigen-presenting cells. With an increase in conformational stability, the T-cell response decreased. However, the reduction was not derived from the inefficiency of internalization to A20 cells nor the alteration of antigenicity by chemical modifications. Moreover, from analyses of their susceptibility to proteolysis and the kinetics of presentation of the T-cell epitope, it was confirmed that increasing protein stability led to the depression of T-cell epitope generation by increasing resistance to proteolysis. These results have an important implication in devising a new strategy for manipulating T-cell response by the stability of protein antigen. An antigen-specific CD4ϩ T-cell recognizes an antigen-derived peptide that is mounted on a major histocompatibility complex class II molecule on a cell surface of antigen-presenting cells, via its antigen receptor (1, 2). Therefore, the conformation of protein antigens is unlikely to have any role in the step of T-cell recognition. Prior to T-cell activation, however, antigen processing is necessary for a protein antigen to stimulate the specific T-cells; this processing consists of multiple steps of cellular events, i.e. internalization of proteins by antigen-presenting cells, reduction of the disulfide bond and unfolding of proteins, enzymatic digestion, and assembly of the generated peptides with major histocompatibility complex class II molecules (3, 4). Proteases preferentially digest proteins in an unfolded state rather than those in a folded state (5-7); thus, the unfolding may be a crucial step for intracellular antigen processing. In this context, we can expect that depression of protein unfolding by increasing protein stability would reduce the antigenicity of proteins for T-cells.Several reports have demonstrated a relationship between increased antigenicity and the decreased stability of proteins (8 -10). However, the influence of protein stability on the antigenicity remains unknown. To address this issue, we prepared three derivatives of hen egg white lysozyme (HEL) 1 possessing different conformational stabilities (see Table I). A three-disulfide derivative of HEL, S-carboxymethylated HEL at Cys ...

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Section: Discussionmentioning

confidence: 99%

Depression of T-cell Epitope Generation by Stabilizing Hen Lysozyme

So¹,

Ito²,

Koga³

et al. 1997

Journal of Biological Chemistry

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“…Thus, in both humans and mice it is apparent that immunization with a nonimmunogenic form of insulin in a permissive MHC haplotype may activate dominant regulatory T cells that recognize autologous insulin. Suppressor T cells may inhibit the ability of helper T cells to stimulate B cells to produce antibodies ( 14), and suppressor T cell lines may block in vitro proliferation of antigen-specific helper T cells (17). L.B.…”

Section: Discussionmentioning

confidence: 99%

Sulfated beef insulin treatment elicits CD8+ T cells that may abrogate immunologic insulin resistance in type I diabetes.

Naquet¹,

Ellis²,

Kenshole³

et al. 1989

J. Clin. Invest.

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“…With reference to cloning, steady progress is being made in defining the conditions under which Ts‐cells can be made to grow in vitro as cell‐lines 5 , and one or two clones possibly representative of Ts‐cells have been described 6 , 7 , 8 . Important conditions are (i) to supply antigen‐presenting cells equipped with appropriate MHC molecules, and (ii) to select on solid‐phase antigen, requirements which, to an extent, contradict one another.…”

Section: Cloningmentioning

confidence: 99%