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

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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

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

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    Roelen, D. L., Stobbe, I., Young, N. T., van Bree, S. P., Doxiadis, I. I., Oudshoorn, M., Morris, P. J., Wood, K. J., & 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