Permissible and immunogenic HLA-A mismatches

cytotoxic T-cell precursor frequencies reflect graft survival data

D L Roelen, I Stobbe, Neil Thomas Young, S P van Bree, I I Doxiadis, M Oudshoorn, P J Morris, K J Wood, F H Claas

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Analysis of the in vivo immunogenicity of single HLA mismatches, in the context of a patient's own human leukocyte antigen (HLA) phenotype, has been used to define permissible and immunogenic HLA mismatches. Kidney graft survival in the case of permissible mismatches was similar to that of completely HLA matched combinations, whereas immunogenic mismatches lead to a significantly poorer graft survival. The present study tested whether such permissible and immunogenic HLA mismatches are reflected in the in vitro cytotoxic T-lymphocyte (CTL) allorepertoire. Limiting dilution experiments were performed to analyze the number of precursor CTL directed against individual HLA class I antigens. In general, the frequency of CTLp directed against permissible HLA-A antigens (n = 70, mean frequency 27 CTLp per million peripheral blood lymphocytes [PBL]) was found to be significantly lower compared with the CTLp directed against immunogenic HLA-A antigens (n = 73, mean frequency 59 CTLp per million PBL). The difference was found both in healthy individuals and a population of renal transplant candidates. These results were confirmed by a retrospective analysis of CTLp frequencies performed between partly mismatched unrelated bone marrow donors and their potential recipients. In conclusion, on the population level the permissible and immunogenic HLA-A mismatches are indeed reflected in the CTL allorepertoire. However, due to the big overlap of the CTLp frequencies in these populations, the permissible or immunogenic nature of a mismatch for a particular patient should be determined on an individual basis.
Original languageEnglish
Pages (from-to)661-667
Number of pages7
JournalHuman Immunology
Volume62
Issue number7
Early online date18 Jun 2001
DOIs
Publication statusPublished - 1 Jul 2001

Fingerprint

T-Lymphoid Precursor Cells
Graft Survival
HLA Antigens
Cytotoxic T-Lymphocytes
Lymphocytes
Population
Kidney
Antigens
Histocompatibility Antigens Class I
Bone Marrow
Tissue Donors
Transplants
Phenotype

Keywords

  • Cells, Cultured
  • Cytotoxicity Tests, Immunologic
  • Graft Survival
  • HLA-A Antigens
  • Histocompatibility Testing
  • Humans
  • Kidney Transplantation
  • Lymphocyte Count
  • Stem Cells
  • T-Lymphocyte Subsets
  • T-Lymphocytes, Cytotoxic

Cite this

Roelen, D. L., Stobbe, I., Young, N. T., van Bree, S. P., Doxiadis, I. I., Oudshoorn, M., ... Claas, F. H. (2001). Permissible and immunogenic HLA-A mismatches: cytotoxic T-cell precursor frequencies reflect graft survival data . Human Immunology, 62(7), 661-667. https://doi.org/10.1016/S0198-8859(01)00263-4

Permissible and immunogenic HLA-A mismatches : cytotoxic T-cell precursor frequencies reflect graft survival data . / Roelen, D L; Stobbe, I; Young, Neil Thomas; van Bree, S P; Doxiadis, I I; Oudshoorn, M; Morris, P J; Wood, K J; Claas, F H.

In: Human Immunology, Vol. 62, No. 7, 01.07.2001, p. 661-667.

Research output: Contribution to journalArticle

Roelen, DL, Stobbe, I, Young, NT, van Bree, SP, Doxiadis, II, Oudshoorn, M, Morris, PJ, Wood, KJ & Claas, FH 2001, 'Permissible and immunogenic HLA-A mismatches: cytotoxic T-cell precursor frequencies reflect graft survival data ', Human Immunology, vol. 62, no. 7, pp. 661-667. https://doi.org/10.1016/S0198-8859(01)00263-4
Roelen, D L ; Stobbe, I ; Young, Neil Thomas ; van Bree, S P ; Doxiadis, I I ; Oudshoorn, M ; Morris, P J ; Wood, K J ; Claas, F H. / Permissible and immunogenic HLA-A mismatches : cytotoxic T-cell precursor frequencies reflect graft survival data . In: Human Immunology. 2001 ; Vol. 62, No. 7. pp. 661-667.
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AU - van Bree, S P

AU - Doxiadis, I I

AU - Oudshoorn, M

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AU - Wood, K J

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AB - Analysis of the in vivo immunogenicity of single HLA mismatches, in the context of a patient's own human leukocyte antigen (HLA) phenotype, has been used to define permissible and immunogenic HLA mismatches. Kidney graft survival in the case of permissible mismatches was similar to that of completely HLA matched combinations, whereas immunogenic mismatches lead to a significantly poorer graft survival. The present study tested whether such permissible and immunogenic HLA mismatches are reflected in the in vitro cytotoxic T-lymphocyte (CTL) allorepertoire. Limiting dilution experiments were performed to analyze the number of precursor CTL directed against individual HLA class I antigens. In general, the frequency of CTLp directed against permissible HLA-A antigens (n = 70, mean frequency 27 CTLp per million peripheral blood lymphocytes [PBL]) was found to be significantly lower compared with the CTLp directed against immunogenic HLA-A antigens (n = 73, mean frequency 59 CTLp per million PBL). The difference was found both in healthy individuals and a population of renal transplant candidates. These results were confirmed by a retrospective analysis of CTLp frequencies performed between partly mismatched unrelated bone marrow donors and their potential recipients. In conclusion, on the population level the permissible and immunogenic HLA-A mismatches are indeed reflected in the CTL allorepertoire. However, due to the big overlap of the CTLp frequencies in these populations, the permissible or immunogenic nature of a mismatch for a particular patient should be determined on an individual basis.

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KW - Cytotoxicity Tests, Immunologic

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KW - Kidney Transplantation

KW - Lymphocyte Count

KW - Stem Cells

KW - T-Lymphocyte Subsets

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