Antigen-specific helper T cells required for dominant production of an idiotype (THId) are not under immune response (Ir) gene control.

Bottomly, Kim; Maurer, Paul H.

doi:10.1084/jem.152.6.1571

Cited by 23 publications

(9 citation statements)

References 34 publications

(72 reference statements)

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“…This proposal is consistent with data indicating that there are two distinct types of helper cells that act synergistically for the induction of optimal antibody responses (27,28,(37)(38)(39)(40). One of these is MHC restricted and has specificity for the immunizing carrier, properties similar to those demonstrated for NP-self Ig-reactive Lyt-1 cells described here.…”

supporting

confidence: 79%

“…One of these is MHC restricted and has specificity for the immunizing carrier, properties similar to those demonstrated for NP-self Ig-reactive Lyt-1 cells described here. Bottomly and co-workers (27,28) have characterized a second antigen-specific helper cell that is not MHC-restricted (27,28). Perhaps hapten-specific helper cells described previously belong to this second category of Proc.…”

mentioning

confidence: 99%

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T-cell proliferative response to hapten-modified self-immunoglobulins: recognition of conjugate-specific determinants.

Bikoff¹

1982

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

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(4-Hydroxy-3-nitrophenyl)acetyl (NP)-modified BALB/c immunoglobulins were used as the immunogen for induction of a proliferative response in BALB/c mice. As is true for responses to other soluble antigens, proliferation was dependent on Lyt-1 cells and histocompatible radioresistant accessory cells. Lyt-1 cells directed against NP-modified self immunoglobulin are specific for the immunizing hapten NP. However, they do not recognize hapten per se. Rather, they see complex determinants comprised ofboth the hapten NP and the immunoglobulin self-carrier. Distinct specificities were created by coupling the same hapten to different monoclonal BALB/c antibody molecules or by attaching the hapten to the immunoglobulin self-carrier via a spacer molecule. It is proposed that determinants created by attaching haptens to self-immunoglobulin molecules are similar to those recognized by anti-idiotypic T cells.Individual T and B lymphocytes recognize unique antigenic determinants via specific receptor molecules on the cell surface. It is generally accepted that antigen receptors on B cells are conventional immunoglobulins (Igs) having the same antigenbinding specificity as secreted antibody molecules. By contrast, there exists a wide range ofopinion regarding the precise chemical structure of the T-cell receptor. In particular, the extent to which antigen receptors on T cells resemble those on B To obtain additional information regarding the possible relationship between T-and B-cell receptors, it would be useful to study T-cell recognition of a simple well-defined antigen-a hapten. Hapten-specific T cells have been extensively described in the literature; the most commonly used strategy for induction of hapten-specific T-cell immunity has been to immunize with the hapten coupled to a self-carrier. One particularly well characterized system is the response to the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP).Anti-NP antibodies produced by C57BL/6 (B6) mice and other strains expressing the b allele at the Igh gene complex express a major crossreactive idiotype (the NPb idiotype) and carry a heteroclytic fine specificity marker; i.e., they have a higher affinity for structurally related haptens such as (4-hydroxy-3-iodo-5 nitrophenyl)acetyl (NIP) than for the immunizing hapten, NP (17, 18). Several populations of NP-specific T cells have been analyzed for expression of these variable region markers. Effector T cells for NP-specific delayed-type hypersensitivity responses express the heteroclytic fine specificity marker (19). NP-specific suppressor cells bear NP" idiotype+ determinants on their surface (11). Soluble heteroclytic NPb idiotype+ receptor material has been isolated from a population of NP-sensitized T cells whose function has not yet been defined (13). By contrast, cytotoxicT lymphocytes directed against NP-coupled autologous cells (20) and NP-specific helper cells (21) express a nonheteroclytic phenotype. These observations are consistent with evidence for structurally distinct receptors on different T-cell...

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supporting

confidence: 79%

mentioning

confidence: 99%

T-cell proliferative response to hapten-modified self-immunoglobulins: recognition of conjugate-specific determinants.

Bikoff¹

1982

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

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“…The second set recognize an Id, and, according to some authors [25], such recognition is independent from the I-A region of the responding cells. Our data suggests a similar mechanism for the suppressive pathway, the only difference being the Igh-C restriction of the Id suppressor cells.…”

Section: Discussionmentioning

confidence: 99%

Idiotype regulation: evidence for the involvement of Igh‐C‐restricted T cells in the M‐460 idiotype suppressive pathway

et al. 1982

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Allotypic restriction of idiotype suppression has been shown in several idiotypic systems. It has also been demonstrated that naive BALB/c mice contain naturally occurring suppressor T cells capable of inhibiting the M-460 idiotype expressed on BALB/c B cells, and that T cells from allotype-congenic mice have no effect on this expression. Since we have previously shown that upon polyclonal activation B cells of all mice tested are capable of secreting M-460-positive anti-2,4,6-trinitrophenyl (TNP) antibodies, we postulated that idiotype suppressor cells may recognize idiotypes in conjugation with products of the Igh loci. In the present study we tested this hypothesis. The data clearly showed that regardless of their allotypic haplotype all strains of mice do possess suppressor cells capable of recognizing the M-460 idiotype. However, mixing experiments indicated that the functional potential of these suppressor cells can only be expressed when T and B lymphocytes come from allotype-matched animals. Efficient suppression in those cultures containing allotype-matched but incompatible B and T cells at the I-J region of the H-2 locus could be detected. Finally, using allotypic recombinant strains of mice, we found evidence that the restrictive elements in idiotypic suppression are the product of genes mapping in the Igh-C locus, or closely linked to it.

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“…Hence, the present data suggest that the specificty of H-2-restricted T cells and their factors is similar. Antigen recognition by nonrestricted factors and T cells (40,41) may also be based on similarities between the respective factors and receptors. Because stringent connection between T cell receptors and factors can he made only when the factor and receptor of the same cell are compared, the problem of nonrestricted factor-producing T cells can be solved only by appropriate cellular antigen-binding assays.…”

Section: Discussionmentioning

confidence: 99%

H-2-restricted helper factor secreted by clone hybridoma cells.

Lonai¹,

Puri²,

Bitton³

et al. 1981

The Journal of Experimental Medicine

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Antigen-specific T helper and T suppressor factors are characterized by their affinity to antigen and by determinants controlled by immunoglobulin heavy chain variable region (Vn) 1 and H-2I loci (for reviews, see 1-3). A generally accepted hypothesis suggests that specific T cell factors may be secreted receptors of T cells. It is interesting, however, that whereas the function of most T cells is H-2 restricted, many antigen-specific T cell factors are not H-2 restricted (4-14). It is not clear, therefore, whether some H-2-restricted T cells produce nonrestricted factors, which thus do not completely represent their receptor, or alternatively, the different factors may respectively represent restricted and nonrestricted T cell sets. Because the difference between regular and associative recognition most likely depends on the nature of the receptor, this problem has important structural and genetic implications. Analysis of the question involves studying H-2 restriction of both the cellular receptor and the helper factor from the same T cell clone. Hybridoma clones secreting H-2-restricted (15) or nonrestricted (11-13) suppressor factors have been described. Much less success was achieved, however, in the construction of helper factor-producing hybridomas, and for neither case is there information that would compare factors and receptors.Recently we have described an approach for the preparation of helper hybridoma cultures (16). One of a number of clones was characterized, and it was shown that this clone, T85-109-45, secretes high titers of carrier, chicken gamma globulin (CGG), specific helper factor. It has also been demonstrated that the T85-109-45 factor contains Ia determinants and also determinants shared with the Ig VH framework

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Antigen-specific helper T cells required for dominant production of an idiotype (THId) are not under immune response (Ir) gene control.

Cited by 23 publications

References 34 publications

T-cell proliferative response to hapten-modified self-immunoglobulins: recognition of conjugate-specific determinants.

T-cell proliferative response to hapten-modified self-immunoglobulins: recognition of conjugate-specific determinants.

Idiotype regulation: evidence for the involvement of Igh‐C‐restricted T cells in the M‐460 idiotype suppressive pathway

H-2-restricted helper factor secreted by clone hybridoma cells.

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