Antigen recognition by MHC-incompatible cells of a human mismatched chimera

M. G. Roncarolo, H. Yssel, J. L. Touraine, R. Bacchetta, L. Gebuhrer, J. E. De Vries, H. Spits

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Abstract

Tetanus toxin (TT)-specific T cell clones of donor origin were obtained from a patient with severe combined immunodeficiency (SCID) successfully reconstituted by transplantation of allogeneic fetal liver and thymus cells from two different donors performed 10 yr ago. A series of these clones recognized TT in the context of 'allo' class II HLA determinants expressed by recipient APC. The restriction element of two T cell clones with the HLA phenotype of the first donor (HLA-DR1,8) and one T cell clone with the HLA phenotype of the second transplant (HLA-DR3,9) was HLA-DR4 of the recipient, whereas other T cell clones derived from the second transplant recognized TT in the context of HLA-DR5 of the recipient's APC. These latter T cell clones were not able to proliferate in response to TT when autologous APC were used. These data demonstrate that recipient and donor cells having different HLA phenotypes could cooperate across the allogeneic barrier and that MHC restriction of antigen (Ag) recognition is independent from the MHC genotype of the T cells but is influenced by the environment in which the T cells mature. We also isolated T cell clones that were able to recognize processed TT presented by all allogeneic EBV cell lines tested, indicating that the Ag specificity of these clones was not restricted by a particular class II MHC molecule. The Ag-specific proliferative response of one of these clones could be blocked by anti-class II MHC mAbs. These results demonstrate that in addition to Ag recognition in the context of specific class II MHC Ags, other types of Ag-specific responses may occur in this human chimera. It is not clear whether this 'allo' plus Ag recognition is the result of education of transplanted fetal cells in the host thymus. Taking into consideration our previous findings indicating that alloreactive T cell clones specific for the recipient cells could be isolated in vitro from the PBL of the same patient, our data suggest that the mechanism for deletion of self-reactive clones and the generation of MHC-restricted responses are different.

Original languageEnglish
Pages (from-to)2139-2152
Number of pages14
JournalJournal of Experimental Medicine
Volume168
Issue number6
Publication statusPublished - 1988

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Clone Cells
Antigens
Tetanus Toxin
T-Lymphocytes
Tissue Donors
Phenotype
Thymus Gland
HLA-DR5 Antigen
HLA-DR1 Antigen
HLA-DR3 Antigen
HLA-DR4 Antigen
Transplants
Severe Combined Immunodeficiency
Homologous Transplantation
Human Herpesvirus 4
Genotype
Education
Cell Line
Liver

ASJC Scopus subject areas

  • Immunology

Cite this

Roncarolo, M. G., Yssel, H., Touraine, J. L., Bacchetta, R., Gebuhrer, L., De Vries, J. E., & Spits, H. (1988). Antigen recognition by MHC-incompatible cells of a human mismatched chimera. Journal of Experimental Medicine, 168(6), 2139-2152.

Antigen recognition by MHC-incompatible cells of a human mismatched chimera. / Roncarolo, M. G.; Yssel, H.; Touraine, J. L.; Bacchetta, R.; Gebuhrer, L.; De Vries, J. E.; Spits, H.

In: Journal of Experimental Medicine, Vol. 168, No. 6, 1988, p. 2139-2152.

Research output: Contribution to journalArticle

Roncarolo, MG, Yssel, H, Touraine, JL, Bacchetta, R, Gebuhrer, L, De Vries, JE & Spits, H 1988, 'Antigen recognition by MHC-incompatible cells of a human mismatched chimera', Journal of Experimental Medicine, vol. 168, no. 6, pp. 2139-2152.
Roncarolo MG, Yssel H, Touraine JL, Bacchetta R, Gebuhrer L, De Vries JE et al. Antigen recognition by MHC-incompatible cells of a human mismatched chimera. Journal of Experimental Medicine. 1988;168(6):2139-2152.
Roncarolo, M. G. ; Yssel, H. ; Touraine, J. L. ; Bacchetta, R. ; Gebuhrer, L. ; De Vries, J. E. ; Spits, H. / Antigen recognition by MHC-incompatible cells of a human mismatched chimera. In: Journal of Experimental Medicine. 1988 ; Vol. 168, No. 6. pp. 2139-2152.
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