T-cell receptor Vβ use predicts reactivity and tolerance to Mlsa- encoded antigens

MacDonald, H. Robson; Schneider, R; Lees, Rosemary K.; Howe, Rawleigh; Acha‐Orbea, Hans; Festenstein, H.; Zinkernagel, Rolf M.; Hengartner, Hans

doi:10.1038/332040a0

Cited by 935 publications

(423 citation statements)

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“…As demonstrated by immunofluorescent staining using mAb 44-22-1 (Fig. 4), a two-to three-fold enrichment of V06+ cells was detectable in BI-specific lines in comparison with the normal level of V06 expression in unimmunized lymph node cells (23). Five of the eight BI-specific lines tested exhibited this enrichment .…”

Section: Resultsmentioning

confidence: 90%

“…DNA prepared from 25 clones was digested with Hind III, Eco RI, and Bam HI, and Southern blots were tested for TCR rearrangements, using a series of oz and (3 TCR probes . 5 of the 25 clones (11,19,14,23, and 28) turned out to be repeated isolates, since they were identical in terms of strain of origin, immunization number, and all primary and secondary TCR rearrangements with another clone (Tables II and III). However, the remaining 20 clones could be unequivocally judged as unique by the same criteria .…”

Section: Resultsmentioning

confidence: 99%

“…Expression of V#6 and V,88 Genes in BI-specific T Cell Clones from (B6 x DBA/2)Fi Mice . The V(06 protein is known to confer reactivity to the product of the Mls-1a gene (23) . Thus, T cells expressing V06 are clonally deleted during establishment of self tolerance to Mls-la .…”

Section: Resultsmentioning

confidence: 99%

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Flexibility of the T cell repertoire. Self tolerance causes a shift of T cell receptor gene usage in response to insulin.

Falcioni¹,

Dembić²,

Müller³

et al. 1990

The Journal of Experimental Medicine

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Bovine insulin(BI)-specific I-Ab-restricted T cell clones have been characterized for fine specificity and TCR gene usage. We have demonstrated that mouse strains carrying H-2b on three different genetic backgrounds (C57BL, BALB, and 129) rearrange and express the V beta 6 gene in a large proportion (36%) of insulin-specific clones. In these strains, the non-MHC background did not seem to influence TCR gene usage in response to BI. The V beta 6+ clones appeared to be selected by the antigen. In contrast, no V beta 6+ clones could be isolated from (B6 x DBA/2)F1 mice, where V beta 6+ (and V beta 8.1+) T cells are deleted by self tolerance to Mls-1a. Thus, although a small proportion of residual V beta 6+ cells had been demonstrated in Mls-1a mice, these cells could not be retrieved in a response that uses V beta 6 predominantly. In functional terms, therefore, the deletion of V beta 6 by self tolerance appears to be complete. Instead of V beta 6, the majority (up to 60%) of I-Ab- as well as I-Ad-restricted insulin-specific clones from the (B6 x DBA/2)F1 mice expressed V beta 8.2 and V beta 8.3. This shift of gene usage was not accompanied by any detectable change in the fine specificity pattern of response. Thus, in the insulin-specific response, the flexibility of T cell repertoire fully compensates for deletions caused by self tolerance.

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Section: Resultsmentioning

confidence: 90%

Section: Resultsmentioning

confidence: 99%

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Flexibility of the T cell repertoire. Self tolerance causes a shift of T cell receptor gene usage in response to insulin.

Falcioni¹,

Dembić²,

Müller³

et al. 1990

The Journal of Experimental Medicine

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“…The results described here will be discussed in the context of pretransplant transfusion effects (20)(21)(22)(23)(24)(25)(26)(27)(28), the veto cell phenomenon first described by Miller and associates (29)(30)(31)(32)(33)(34)(35)(36), and the concept of peripheral tolerance as opposed to tolerance induced by intrathymic clonal deletion ofantigen-reactive T lymphocytes (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11) to active suppression, but due to clonal paralysis of antigenreactive Lyt-2+ CTIrp-and 11,2-producing Lyt-2+ T cells . Since donor lymphocytes exhibit clonal anergy to recipient class I MHC antigens, yet express in vitro remarkably efficient veto functions, we believe that the reciprocal peripheral tolerance in the adult chimeric mice is caused, and maintained, by veto activity of donor and recipient cells.…”

Section: Discussionmentioning

confidence: 99%

“…This conversion is successful in neonates: introduction of foreign antigens into a developing immune system prevents the system from responding further on to these antigens (1,2). Recent evidence indicates that both in natural tolerance and in experimentally induced neonatal unresponsiveness maturing antigen-reactive thymocytes become either clonally deleted (3)(4)(5)(6)(7)(8) or at least clonally silenced (9)(10)(11) .…”

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confidence: 99%

Induction of peripheral tolerance to class I major histocompatibility complex (MHC) alloantigens in adult mice: transfused class I MHC-incompatible splenocytes veto clonal responses of antigen-reactive Lyt-2+ T cells.

Heeg

Wagner

1990

The Journal of Experimental Medicine

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SummaryThe efficacy and the mode ofaction of pretransplant transfusion with class I major histocompatibility complex (MHC)-disparate splenocytes in establishing a state of peripheral tolerance in adult mice is analyzed. Adult mice injected intravenously with a critical number of N5 x 10' allogenic splenocytes accept skin grafts and develop chimerism in the peripheral lymphatic tissues, but not in thymus and bone marrow. In parallel, a split tolerance evolves : the frequency of class I MHC-reactive Lyt-2+ cytotoxic T lymphocyte precursor (CTIrp)-and interleukin 2 (IIr2)-producing T cells falls off in the peripheral lymphoid tissue, but remains unaltered intrathymically. In particular, high affinity CTLp become clonally undetectable . In vivo generation of tolerant cells is cyclosporin A resistant, but dependent on recipient L3T4+ T cells. Loss of Lyt-2+ CTIrpand IL-2-producing T cell precursors is not due to active suppression, but is caused by clonal anergy. Donor-derived chimeric cells positively selected 7 d after intravenous transfusion exhibit in vitro the hallmarks of veto cells, i.e., paralyze CTLp reactive to donor-type class I MHC alloantigens . We conclude that the peripheral (split) tolerance induced in vivo by pretransplant transfusion operates because donor-type cells develop in vivo efficiently into "veto cells;' which in turn induce a state of clonal anergy within antigen-reactive Lyt-2+ T lymphocytes.A prime aim in transplantation immunology is to define gentle methods able to convert immune reactivity to transplantation antigens into a state of immune unresponsiveness. This conversion is successful in neonates: introduction of foreign antigens into a developing immune system prevents the system from responding further on to these antigens (1, 2). Recent evidence indicates that both in natural tolerance and in experimentally induced neonatal unresponsiveness maturing antigen-reactive thymocytes become either clonally deleted (3-8) or at least clonally silenced (9-11) .Induction of unresponsiveness in a mature peripheral T cell pool meets difficulties : receptor occupancy by antigens primarily induces sensitization rather than tolerization (12)(13)(14) . Therefore, most strategies attempt first to reduce the pool of immunocompetent peripheral T lymphocytes, and thereafter to induce unresponsiveness by exposing the regenerating (neonatal) immune system to antigen . In the first step, rather invasive techniques are used, such as whole body (15, 16) or total lymphoid irradiation (17), systemic application of antiproliferative drugs (18,19), or a combination of either of these methods.Evaluation of pretransplant transfusion effects have indicated that intravenous confrontation with allogeneic cells may induce specific immunosuppression rather than sensitization (20)(21)(22)(23)(24)(25)(26)(27)(28) Miller, Bevan, pioneered the veto cell concept . Accordingly, unlinked to the specificity of their own antigen receptor, veto cells paralyze in vitro the response of T cells reacting to antigens displayed by ...

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Superantigens. Do they have a role in skin diseases?

Skov

Baadsgaard²

1995

Archives of Dermatology

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T-cell receptor Vβ use predicts reactivity and tolerance to Mlsa- encoded antigens

Cited by 935 publications

References 51 publications

Flexibility of the T cell repertoire. Self tolerance causes a shift of T cell receptor gene usage in response to insulin.

Flexibility of the T cell repertoire. Self tolerance causes a shift of T cell receptor gene usage in response to insulin.

Induction of peripheral tolerance to class I major histocompatibility complex (MHC) alloantigens in adult mice: transfused class I MHC-incompatible splenocytes veto clonal responses of antigen-reactive Lyt-2+ T cells.

Superantigens. Do they have a role in skin diseases?

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