Role of donor and recipient antigen-presenting cells in priming and maintaining t cells with indirect allospecificity

Loredana Frasca, Alessandra Amendola, Phil Hornick, Paul Brookes, Gerald Aichinger, Federica Marelli-Berg, Robert Ian Lechler, Giovanna Lombardi

Research output: Contribution to journalArticle

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Abstract

Background. It has been suggested that the sensitization of recipient T lymphocytes against peptides derived from allogeneic major histocompatibility complex (MHC) antigens in the context of self-MHC molecules may contribute to the pathogenesis of chronic allograft rejection. The purpose of this study was to quantitate and characterize the indirect alloresponse in renal transplantation. Methods. An HLA-A2-negative patient whose A2-positive kidney transplant failed as a result of chronic rejection was selected for this study. T-cell clones were raised using a cocktail of peptides corresponding to polymorphic regions of the A2 sequence and studied by measuring their proliferation using [3H]thymidine incorporation. The presence in vivo of HLA-A2-specific T cells was assessed using limiting dilution analysis. Results. T-cell clones were specific for a single peptide of HLA-A2, residues 92-120, and restricted by HLA-DRB1*1502. The frequency of interleukin-2- secreting T cells specific for this A2 peptide was 1:86,000, only 2-fold lower than that measured against the recall antigen tetanus toxoid. Capitalizing on the similarity of the donor and recipient DR15 alleles (DRB1*1501 and 1502), the question was addressed as to how these T cells had been primed in vivo. Although the large majority of clones responded to A2 synthetic peptide presented by both DR15 alleles, only 3 of 10 clones responded to cells co-expressing DRB1*1501 and A2. Conclusion. These data suggest that antigen presentation by recipient APCs is responsible for maintaining T cells with indirect allospecificity in vivo and that, in the context of partial DR matching, indirect presentation by the parenchymal cells of the graft may serve to induce tolerance in T cells with indirect allospecificity.

Original languageEnglish
Pages (from-to)1238-1243
Number of pages6
JournalTransplantation
Volume66
Issue number9
Publication statusPublished - Nov 15 1998

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Antigen-Presenting Cells
Tissue Donors
T-Lymphocytes
varespladib methyl
HLA-A2 Antigen
Clone Cells
Peptides
Major Histocompatibility Complex
Alleles
Transplants
HLA-DRB1 Chains
Tetanus Toxoid
Histocompatibility Antigens
Antigen Presentation
Kidney Transplantation
Thymidine
Interleukin-2
Allografts
Kidney
Antigens

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Frasca, L., Amendola, A., Hornick, P., Brookes, P., Aichinger, G., Marelli-Berg, F., ... Lombardi, G. (1998). Role of donor and recipient antigen-presenting cells in priming and maintaining t cells with indirect allospecificity. Transplantation, 66(9), 1238-1243.

Role of donor and recipient antigen-presenting cells in priming and maintaining t cells with indirect allospecificity. / Frasca, Loredana; Amendola, Alessandra; Hornick, Phil; Brookes, Paul; Aichinger, Gerald; Marelli-Berg, Federica; Lechler, Robert Ian; Lombardi, Giovanna.

In: Transplantation, Vol. 66, No. 9, 15.11.1998, p. 1238-1243.

Research output: Contribution to journalArticle

Frasca, L, Amendola, A, Hornick, P, Brookes, P, Aichinger, G, Marelli-Berg, F, Lechler, RI & Lombardi, G 1998, 'Role of donor and recipient antigen-presenting cells in priming and maintaining t cells with indirect allospecificity', Transplantation, vol. 66, no. 9, pp. 1238-1243.
Frasca L, Amendola A, Hornick P, Brookes P, Aichinger G, Marelli-Berg F et al. Role of donor and recipient antigen-presenting cells in priming and maintaining t cells with indirect allospecificity. Transplantation. 1998 Nov 15;66(9):1238-1243.
Frasca, Loredana ; Amendola, Alessandra ; Hornick, Phil ; Brookes, Paul ; Aichinger, Gerald ; Marelli-Berg, Federica ; Lechler, Robert Ian ; Lombardi, Giovanna. / Role of donor and recipient antigen-presenting cells in priming and maintaining t cells with indirect allospecificity. In: Transplantation. 1998 ; Vol. 66, No. 9. pp. 1238-1243.
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AU - Hornick, Phil

AU - Brookes, Paul

AU - Aichinger, Gerald

AU - Marelli-Berg, Federica

AU - Lechler, Robert Ian

AU - Lombardi, Giovanna

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