Selective participation of immunoglobulin V region and major histocompatibility complex products in antigen binding by T cells

Lonai, Peter; Ben‐Neriah, Yinon; Steinman, Lawrence; Givol, David

doi:10.1002/eji.1830081202

Cited by 60 publications

(34 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, anti-Vx and anti-V, did not retain helper activity, and all of the activity appeared in the column effluent. These data are in agreement with a number of other results obtained with our anti-VH region reagents (24)(25)(26) or with anti-idiotypic antibodies (27)(28)(29).…”

Section: Resultssupporting

confidence: 93%

“…The reagents used in these experiments were extensively characterized by serological (21-23) as well as functional experiments. It has been shown that anti-Vn but not anti-VL inhibits antigen binding by Lyt-1 +,2-,3-normal lymphocytes (24); that anti-Vn but not anti-Vx inhibits streptococcal carbohydrate-specific helper cells (25), and also that anti-Vn but not anti-Vx or anti-V~ protects helper T cells from radioactive antigen "suicide" (26). Additional studies have shown that anti-Vn binds the Ig-receptor of hapten-specific T cells (30), that it interferes with the binding of membrane receptors by allostimulated T cells (31), and that it is present on the (32) and helper-factor-producing hybridomas (33).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Lonai¹,

Puri²,

Bitton³

et al. 1981

The Journal of Experimental Medicine

View full text Add to dashboard Cite

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

show abstract

Section: Resultssupporting

confidence: 93%

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

View full text Add to dashboard Cite

show abstract

“…Previous experiments have demonstrated that IAC contains Ia antigens and that it is bound by helper T cells via receptors that share determinants with the "framework" of immunoglobulin VH (7,13,14). This was confirmed by the inhibition ofbinding in the presence of3 pug of anti-V11 and by the loss ofbinding activity in the IAC preparation after it was passed through an anti-IakSepharose column.…”

Section: Methodsmentioning

confidence: 68%

H-2-restricted antigen binding by a hybridoma clone that produces antigen-specific helper factor.

Lonai¹,

Puri²,

Hämmerling³

1981

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

View full text Add to dashboard Cite

Somatic cell hybrids were prepared by fusing the AKR mouse lymphoma BW-5147 with splenic T cells from mice immunized with 4-hydroxy-3-nitrophenylacetic acid (NP) conjugated to chicken serum globulin (CG). From 500 fusion lines 11 were selected on the basis of binding radioiodinated NP-CG. The autoradiographic bindin' assay was based on previous findings which showed that Lyt-1 T cells need a lymphokine, lymphocyteactivating factor (LAF), for optimal antigen binding and that they bind preferentially a self-la-associated antigen complex, IAC, which is released by adherent cells upon incubation with antigen. Six of the 11 antigen-binding positive lines were tested for helper activity and specific helper actor production in vitro All of them were found to be positive. One clone was characterized in more detail. It secretes a CG-specific helper factor that contains immunoglobulin heavy chain variable region and I-A determinants. The hybridoma cells bind Ia-containing CG complexes specifically. For binding they need to be treated with LAF, and the binding is restricted to syngenicity in H-2 between the adherent cells used to produce LAC and the antigen-binding hybridoma cells.Regular CG does not bind significantly and does not compete even at high excess with the binding of CG-IAC. These data are interpreted to suggest that the antigen is bound by cells of a cloned functional helper T-cell hybridoma line in conjunction with products controlled by H-2I and that the receptor of these cells may have considerably higher affinity for la-associated than for regular antigen.Immunocytes respond to a very large number of different antigens, and it is generally accepted that each clone recognizes a particular antigenic determinant. Therefore, molecular analysis of immunocyte receptors as well as their ligands-the latter being of special interest in the case of the "H-2-restricted" T cells-largely depends on the availability ofhomogeneous lymphocyte lines. Somatic cell hybridization was extensively used for this end, and hybrids between antibody-forming lymphocytes and myeloma tumor cells are widely used for the production of monoclonal antibodies (1). Hybridization of T lymphocytes with thymoma cells is also possible (2), and a number of functional suppressor T-cell hybridoma lines have already been described (3-6). It is striking that most functional T hybrids reveal suppressor activity, whereas it appears more difficult to isolate T hybrids with specific helper function.Here we report the use ofautoradiographic antigen binding, based on preferential binding ofIa-associated antigens (IAC) by helper cells (7), for the selection ofhelper hybrid lines. Hybrids selected for their antigen-binding property were further tested for helper activity. The specific helper factor produced by cells of a clone isolated from one of these lines and the antigenbinding properties of the cloned hybridoma cells are described below. MATERIALS AND METHODSPreparation of T-Cell Hybridoma Lines. These lines were prepared according to Hammerlin...

show abstract

“…T cells which mediate delayed-type hypersensitivity (TDn) (16) and helper T cells (17) recognize antigen in association with I region-encoded determinants. Furthermore, Lonai and co-workers (18) had reported that antigen binding to Lyt-1 + cells was inhibited by anti-VH antiserum, whereas antigen binding to Lyt2+3 + ceils were inhibited by anti-VL specifically.…”

mentioning

confidence: 99%

Antigen- and receptor-driven regulatory mechanisms. III. Induction of delayed type hypersensitivity to azobenzenearsonate with anti-cross-reactive idiotypic antibodies.

Sy¹,

Brown²,

Benacerraf³

et al. 1980

The Journal of Experimental Medicine

View full text Add to dashboard Cite

Delayed-type hypersensitivity (DTH) to p-azobenzenearsonate (ABA) can be induced in A/J mice with intravenous injection of minute amounts of anti-cross-reactive idiotypic (CRI) antibodies, providing that the animals have been pretreated 2 d earlier with low doses of cyclophosphamide (50 mg/kg). However intravenous injection of the F(ab')2 fragments of the anti-CRI antibodies or subcutaneous administration with anti-CRI antibodies induces comparable immunity in both cyclophosphamide-pretreated and normal nontreated animals. Furthermore adoptive transfer experiments indicate that lymph node cells taken from animals sensitized with anti-CRI 4 d earlier can adoptively transfer immunity to naive recipients. Transfer of immunity is mediated by a population of thymus-dependent (T) cells, which express idiotypic structures on their surface. Treatment of effector cells with either anti-theta serum or anti-idiotypic antibodies plus complement completely abrogated their ability to transfer immunity. In addition idiotype-bearing suppressor T cells induced with ABA-coupled spleen cells inhibit the development of ABA-specific DTH induced with anti-CRI antibodies. Genetic analysis revealed that the ability of anti-CRI antibodies to induce ABA-specific DTH was linked to Igh-1 heavy-chain allotype. Anti-idiotypic antibodies to the major CRI associated with anti-ABA antibodies in A/J mice failed to induce significant immunity in BALB/c mice (H-2d, Igh-1a). Nevertheless, they were able to induce significant immunity in C.AL20 mice (H-2d, Igh-1d) which possess a heavy-chain allotype similar to that of A/J mice.

show abstract

Selective participation of immunoglobulin V region and major histocompatibility complex products in antigen binding by T cells

Cited by 60 publications

References 24 publications

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

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

H-2-restricted antigen binding by a hybridoma clone that produces antigen-specific helper factor.

Antigen- and receptor-driven regulatory mechanisms. III. Induction of delayed type hypersensitivity to azobenzenearsonate with anti-cross-reactive idiotypic antibodies.

Contact Info

Product

Resources

About