Permissible and immunogenic HLA-A mismatches: Cytotoxic T-cell precursor frequencies reflect graft survival data

Analysis of the in vivo immunogenicity oi single HLA mismatches, in the con text of a patient's own human leukocyte antigen (HLA) phenotype, has been u sed to define permissible and immunogenic HLA mismatches, Kidney graft surv ival in the case of permissible mismatches was similar to that of completel y HLA matched combinations, whereas immunogenic mismatches lead to a signif icantly poorer graft survival. The present study rested whether such permis sible and immunogenic HLA mismatches are reflected in the in vitro cytotoxi c T-lymphocyte (CTL) allorepertoire. Limiting dilution experiments were per formed to analyze the number of precursor CTL directed against individual H LA class I antigens. In general, the frequency of CTLp directed against per missible HLA-A antigens (n = 70, mean frequency 27 CTLp I,cr million periph eral blood lymphocytes [PBL]) was found to be significantly lower compared with the CTLp directed against immunogenic HLA-A antigens (n = 73, mean fre quency 59 CTLp per million PBL). The difference was found both in healthy i ndividuals and a population of renal transplant candidates. These results w ere confirmed by a retrospective analysis of CTLp frequencies performed bet ween partly mismatched unrelated bone marrow donors and their potential rec ipients. In conclusion, on the population level the permissible and immunog enic HLA-A mismatches are indeed reflected in the CTL allorepertoire. Howev er, due to the big overlap of the CTLp frequencies in these populations, th e permissible or immunogenic nature of a mismatch for a particular patient should be determined on an individual basis. Human Immunology 62, 661-667 ( 2001). (C) American Society for Histocompatibility and Immunogenetics, 2001 . Published by Elsevier Science Inc.