Alloreactive cytolytic T-cell clones preferentially recognize conformational determinants on histocompatibility antigens: analysis with genetically engineered hybrid antigens.

Arnold, Bernd; Horstmann, Ulrike; Kuon, Wolfgang; Burgert, Hans‐Gerhard; Hämmerling, Günter J.; Kvist, Sune

doi:10.1073/pnas.82.20.7030

Cited by 63 publications

(41 citation statements)

References 19 publications

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“…Alloreactive CTLs were generated in mixed lymphocyte cultures as described (14). Target Cells and Cytolytic Assays.IC9 fibrosarcoma cells (15) were infected with 1 plaque-forming unit per cell of vaccinia virus strain Copenhagen. After 2 hr, the inoculum was removed, fresh medium was added, and cells were incubated overnight (12-18 hr).…”

Section: Methodsmentioning

confidence: 99%

Transgenic mice expressing a soluble foreign H-2 class I antigen are tolerant to allogeneic fragments presented by self class I but not to the whole membrane-bound alloantigen.

Arnold

Messerle

Jatsch

et al. 1990

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

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The properties of transmembrane and soluble transplantation antigens were compared with respect to the induction of tolerance and the selection of the T-cell repertoire.For this purpose, transgenic (H-2b X H-2d)F1 mice were constructed that carry integrated copies of a modified H-2Kk gene resulting in the secretion from various cell types including thymocytes of soluble H-2Kk molecules. Despite the presence of H-2Kk antigen, these mice were still able to generate an H-2Kk-specific T-cell response. This response was comparable to that produced by normal littermates when stimulated with cells expressing membrane H-2Kk in a mixed lymphocyte reaction. In contrast, only transgenic mice failed to generate a cytolytic T-cell response to soluble H-2Kk antigen expressed by recombinant vaccinia virus and presented by the H-2Db molecule. These data imply the presence of two populations of alloreactive cytolytic T cells. A small fraction of T cells recognizes alloantigen as antigenic peptide(s) presented by other major histocompatibility complex class I molecules and tolerance can be induced in this population by soluble alloantigen. The majority of T cells, however, require the whole cell membrane-expressed class I molecule for recognition. This population is not affected by tolerance induction to the soluble major histocompatibility complex class I molecule.

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Section: Methodsmentioning

confidence: 99%

Transgenic mice expressing a soluble foreign H-2 class I antigen are tolerant to allogeneic fragments presented by self class I but not to the whole membrane-bound alloantigen.

Arnold

Messerle

Jatsch

et al. 1990

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

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“…anti-H-2D b (K7-65, mIgG2a) [28], anti-I-A d (K24-199, mIgG2a), and anti-I-A b (K25-137, mIgG2A) [29] were kindly provided by G. Hämmerling, Department of Immunogenetics, German Cancer Research Center. Rat IgG and culture supernatant-derived mAb were purified by passage over Protein A-or Protein G-Sepharose [30,31].…”

Section: Antibodiesmentioning

confidence: 99%

Treatment of mice with anti-CD44 after allogeneic bone marrow cell transplantation is lethal

Zöller

Föhr

Herrmann

1998

Journal of Leukocyte Biology

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Because CD44 is known to be of functional importance in hematopoiesis, we were interested in whether anti-CD44 would interfere with syngeneic or allogeneic bone marrow cell engraftment. Syngeneic and allogeneic grafts were accepted by over 80% of mice. In both the syngeneic and the allogeneic host, homing, repopulation, and regain of immunoreactivity was delayed by anti-CD44 treatment. But in the syngeneic host the overall survival rate was unaltered. Instead, less than 25% of anti-CD44-treated, allogeneically reconstituted mice survived by recovery of the host's hematopoietic system, i.e. graft acceptance was close to 0%. The mice died between 4 and 15 days after engraftment and showed severe alterations of the gut. The high death rate of the allogeneically reconstituted mice was specific for anti-CD44 treatment. It did not depend on an ADCC mechanism, could not be abrogated by depletion of T cells, and was only mitigated by depletion of NK cells. According to the histological appearance of the gut, anti-CD44 strengthens a local (gut-associated) graft versus host reaction, which is not mediated by ␣␤ T cells and at least not exclusively by NK cells. Because gut death is one of the major reasons for failure in allogeneic bone marrow transplantation, the model of anti-CD44-induced lethality offers itself to clarify the underlying mechanism.

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“…H2 -D b (K7-65)-and H2-A b (K25 -137 )-specific mAb 56,57 were kindly provided by G. Hämmerling ( German Cancer Research Center, Heidelberg, Germany ). Anti-CD28, anti -CD40, anti -CD40L, anti -CD80, anti-CD86, anti -CD152, anti -IL2, anti -IL4, anti -IL6, anti-IL10, anti -IL12, anti -IFN , anti -TNF , and secondary, dye -labeled (FITC, Rhodamin, or PE ) antibodies were obtained commercially (Pharmingen, Hamburg, Germany ).…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

Gene delivery by attenuated Salmonella typhimurium : Comparing the efficacy of helper versus cytotoxic T cell priming in tumor vaccination

Weth

Christ

Stevanović³

et al. 2001

Cancer Gene Ther

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Using the murine B16F1 melanoma, we compared a CTL -versus helper T cell ( TH ) -directed vaccination approach. Mice were either orally vaccinated with attenuated Salmonella typhimurium ( SL ) or subcutaneously with dendritic cells ( DCs ) loaded with gp100 peptides predicted to bind to H2 -Kb / H2 -Db molecules. SL were transformed with the murine gp100 cDNA ( SL -gp100 ) or with a fusion construct of gp100 and a fragment of invariant chain cDNA ( SL -gp100 / Ii ). Transcription of these genes in vivo has been readily observed in monocytes and DC. Retardation of B16F1 growth was more efficiently achieved by vaccination with SLgp100 than with DC. Vaccination with SL -gp100 / Ii aiming at preferential presentation by MHC II molecules provided some further improvement due to a stronger expansion of TH and CTL. The importance of help was further sustained by a prolongation of the survival time when mice concomitantly received IL2. Notably, prophylactic, compared to therapeutic, vaccination had no additional impact on survival time / rate. This was due to a striking decrease in frequencies of gp100 -specific TH, CTL, and cytokine -expressing cells during tumor growth. Thus, the efficacy of vaccination was limited by tumor -induced immunosuppression. Our data demonstrate the oral route of vaccination via Salmonella as a most convenient transfer regimen and confirm the superiority of protocols aiming at preferential activation of TH. Cancer Gene Therapy ( 2001 ) 8, 599 -611

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Alloreactive cytolytic T-cell clones preferentially recognize conformational determinants on histocompatibility antigens: analysis with genetically engineered hybrid antigens.

Cited by 63 publications

References 19 publications

Transgenic mice expressing a soluble foreign H-2 class I antigen are tolerant to allogeneic fragments presented by self class I but not to the whole membrane-bound alloantigen.

Transgenic mice expressing a soluble foreign H-2 class I antigen are tolerant to allogeneic fragments presented by self class I but not to the whole membrane-bound alloantigen.

Treatment of mice with anti-CD44 after allogeneic bone marrow cell transplantation is lethal

Gene delivery by attenuated Salmonella typhimurium : Comparing the efficacy of helper versus cytotoxic T cell priming in tumor vaccination

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