Lymphocytotoxic antibodies produced by H—2 allo-immunisation distinguish between MuLV-positive and -negative substrains of the same H-2 haplotype

Iványi, P; Melief, Cornelis J.M.; Mourik, Peter van; Vlug, A.; Greeve, Paul de

doi:10.1038/282843a0

Cited by 16 publications

(4 citation statements)

References 11 publications

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“…However, humoral tolerance to third-party cells was surprising in that an alloantibody response to private specificities might have been expected. This suggests that humoral tolerance may involve a dominant tolerance mechanism (e.g., Ab feedback through FcR (58) or Treg cells) to public specificities on MHC or additional Ags (57,59) and not simply deletion of donor-specific B cells (60). Although cross-reactive alloimmunity has been well demonstrated, we are not aware of any published data showing that humoral tolerance to one donor can extend to additional donors.…”

Section: Discussionmentioning

confidence: 70%

Development of Either Split Tolerance or Robust Tolerance along with Humoral Tolerance to Donor and Third-Party Alloantigens in Nonmyeloablative Mixed Chimeras

Chan¹,

Razavy

Luo

et al. 2008

The Journal of Immunology

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Hematopoietic chimerism is considered to generate robust allogeneic tolerance; however, tissue rejection by chimeras can occur. This “split tolerance” can result from immunity toward tissue-specific Ags not expressed by hematopoietic cells. Known to occur in chimeric recipients of skin grafts, it has not often been reported for other donor tissues. Because chimerism is viewed as a potential approach to induce islet transplantation tolerance, we generated mixed bone marrow chimerism in the tolerance-resistant NOD mouse and tested for split tolerance. An unusual multilevel split tolerance developed in NOD chimeras, but not chimeric B6 controls. NOD chimeras demonstrated persistent T cell chimerism but rejected other donor hematopoietic cells, including B cells. NOD chimeras also showed partial donor alloreactivity. Furthermore, NOD chimeras were split tolerant to donor skin transplants and even donor islet transplants, unlike control B6 chimeras. Surprisingly, islet rejection was not a result of autoimmunity, since NOD chimeras did not reject syngeneic islets. Split tolerance was linked to non-MHC genes of the NOD genetic background and was manifested recessively in F1 studies. Also, NOD chimeras but not B6 chimeras could generate serum alloantibodies, although at greatly reduced levels compared with nonchimeric controls. Surprisingly, the alloantibody response was sufficiently cross-reactive that chimerism-induced humoral tolerance extended to third-party cells. These data identify split tolerance, generated by a tolerance-resistant genetic background, as an important new limitation to the chimerism approach. In contrast, the possibility of humoral tolerance to multiple donors is potentially beneficial.

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Section: Discussionmentioning

confidence: 70%

Development of Either Split Tolerance or Robust Tolerance along with Humoral Tolerance to Donor and Third-Party Alloantigens in Nonmyeloablative Mixed Chimeras

Chan¹,

Razavy

Luo

et al. 2008

The Journal of Immunology

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“…It has been suggested that neodeterminants, which result from molecular association of MHC and foreign antigens, might also be recognized by antibodies. Such reports are not frequent and refer to MHC and influenza virus [ll], SV40 [40], TNP 1131, human H-Y [12] and murine leukemia virus [14] antigens.…”

Section: Recognition Of Foreign Antigens By B and T Cellsmentioning

confidence: 99%

“…Such antibodies were capable of highly specific recognition of antigenic determinants in the context of syngeneic MHC. Other studies have reported that anti-H-2 antibodies can recognize modifications induced by 2,4,6-trinitrophenyl (TNP) [13] or bind to syngeneic virus-infected cells [14]. Furthermore, MHC-specific antibodies have been found in nonimmunized mice or in mice injected with syngeneic cells [18][19][20].…”

Section: Introductionmentioning

confidence: 98%

Induction of H‐2‐specific antibodies by injections of syngeneic Sendai virus‐coated cells

et al. 1987

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The capacity of the B cell immunoglobulin receptor to recognize complexes of Sendai viral and H-2b antigens was investigated by studying the antibody response to injections of syngeneic Sendai virus-coated (SV+) spleen cells in C57BL/6 (B6) mice. Almost all mice produced alloreactive anti-H2 lymphocytotoxic antibodies. In contrast, such antibodies were found very exceptionally in mice injected with normal (SV-) cells or with Sendai virus (SV) only. The reaction pattern of the cytotoxic antibodies induced was variable and ranged from almost anti-private to widely cross-reactive serotypes. The results of reactions on H-2-congenic, -recombinant and -mutant mouse strains, and of capping and immunoprecipitation experiments showed that the cytotoxic antibodies were directed against H-2 class I molecules. The anti-H-2 antibodies exhibited enhanced binding for SV+ target cells, but absorption experiments showed that this was not the result of cross-reactions with cell surface Sendai viral determinants or with a molecular complex of H-2 plus SV. This conclusion was supported by the observation that syngeneic SV+ cells were not the predominant targets for the induced lymphocytotoxic antibodies. Our results do not support the existence of MHC-restricted antiviral antibodies, but show the induction of anti-class I H-2 alloantibodies by injections with syngeneic SV-coated cells. We present a model for regular induction of anti-H-2 antibodies without intentional alloimmunization.

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“…All hitherto obtained results suggest that the target molecules are not the classical H-2 antigens but other membrane structures controlled by the H-2 complex. Whereas the exact nature of the target structure(s) and its polymorphism remain unknown, circumstantial evidence discussed in the preceding paragraphs points to the possibility that the virus status of individual mice (14,19,20) is decisive for the lymphocyte antigen expression (21) influenced by the H-2 complex.…”

mentioning

confidence: 99%

Naturally occurring cytotoxic human antibodies recognize H-2-controlled murine lymphocyte antigens.

Iványi¹,

Leupers²,

Mourik³

1983

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

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Human sera contain cytotoxic naturally occurring (CyNa) antibodies which discriminate between lymph node cells from mice differing only at the H-2 complex. Sera from three healthy subjects (normal human sera, NH sera) and one serum from a patient with multiple sclerosis reacted with cells expressing Db, Kd, Kk, and KP molecules, respectively. However, the following observations suggested that the binding specificity of these CyNa antibodies is to antigens that are distinct from the classical H-2 antigens: (i) the NH sera did not contain cytotoxic anti-HLA antibodies, (ii) redistribution (capping) of H-2 antigens did not induce resistance to lysis for CyNa antibodies, and (iii) individual variation was demonstrated in the expression of the murine lymphocyte antigens detected by the human CyNa antibodies. The reason for this variation appeared to be different for individual NH serum. A maternal effect influenced the expression of the murine lymphocyte antigen detected by one NH serum (anti-H2b). The differences detected by another NH serum (anti-H-2P) appeared to be inherited, as shown by progeny testing. We hypothesize that the human CyNa antibodies may be directed against antigens controlled or modified by murine viruses (milk borne or endogenous), whose expression is under the influence of the H-2 complex, and that their production might have been stimulated by the products of human genes homologous to murine viruses.Human and animal sera contain cytotoxic "natural" antibodies (CyNa Abs) against lymphocytes from individuals of other species. Such antibodies are designated as nonspecific, speciesspecific, or heterophile. Studies on CyNa Abs are scarce and do not provide a conclusive explanation of their origin and specificity. It is not known (i) whether such antibodies are triggered by exogenous antigens or altered-self structures, (ii) what their target molecules are, (iii) what the reasons are for the species and individual variability in their occurrence and specificity, and (iv) whether they have biological relevance (1-4). Studies on CyNa Abs are hampered by their low titers and avidity, temperature sensitivity, and possible polyvalent nature. Only scant data are available about human CyNa Abs in sera of nontransfused male blood donors (normal human sera; NH sera). Such sera were used as controls in studies with hyperimmune anti-HLA antisera against panels of murine lymphocytes and were found to be either negative (5) or weakly positive (6) and did not distinguish normal murine lymphocytes carrying diferent H-2 haplotypes. One NH serum was found that distinguished, after absorptions, chicken erythrocytes with different major histocompatibility complex antigens (7).We tested a large number of NH sera and sera from diseased individuals on a panel of lymph node cells from congeneic mouse strains differing only at the major histocompatability complex.

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Lymphocytotoxic antibodies produced by H—2 allo-immunisation distinguish between MuLV-positive and -negative substrains of the same H-2 haplotype

Cited by 16 publications

References 11 publications

Development of Either Split Tolerance or Robust Tolerance along with Humoral Tolerance to Donor and Third-Party Alloantigens in Nonmyeloablative Mixed Chimeras

Development of Either Split Tolerance or Robust Tolerance along with Humoral Tolerance to Donor and Third-Party Alloantigens in Nonmyeloablative Mixed Chimeras

Induction of H‐2‐specific antibodies by injections of syngeneic Sendai virus‐coated cells

Naturally occurring cytotoxic human antibodies recognize H-2-controlled murine lymphocyte antigens.

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