AUTHOR=Israeli Moshe , Roelen Dave L. , Carrington Mary , Petersdorf Effie Wang , Claas Frans H. J. , Haasnoot Geert W. , Oudshoorn Machteld 

TITLE=Association between CTL Precursor Frequency to HLA-C Mismatches and HLA-C Antigen Cell Surface Expression

JOURNAL=Frontiers in Immunology

VOLUME=5

YEAR=2014

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2014.00547

DOI=10.3389/fimmu.2014.00547

ISSN=1664-3224

ABSTRACT=<p>Previous studies showed the relevance of the cytotoxic T-cell precursor (CTLp) frequency assay for prediction of the outcome of HLA mismatched hematopoietic cell transplantation (HCT). Recently, it has been shown that HLA-C cell surface expression is correlated with virus specific cytotoxic T-cell responses and viremia control in HIV patients. The aim of the current study was to investigate the association between HLA-C antigen expression and the CTLp frequency to the mismatched HLA-C antigen. In total 115 recipient–donor pairs, for whom a successful CTLp assay was performed, were evaluated for this pilot study. All donor–recipient pairs were matched at 9/10 alleles with a single mismatch at the HLA-C locus. Antigen expression level of the mismatched HLA-C allele for each recipient and donor was based on the mean fluorescence intensity (MFI) values as described by Apps et al. (<xref ref-type="bibr" rid="B1">1</xref>). The cell surface expression of recipient’s mismatched HLA-C antigen was significantly lower among CTLp negative (<italic>n</italic> = 59) compared to CTLp positive (<italic>n</italic> = 56) pairs (154 and 193 MFI units, respectively, <italic>p</italic> = 0.0031). This difference was more pronounced in donor–recipient pairs that were mismatched for amino-acid residue-116 located in the groove of the HLA-C antigen, suggesting that the importance of peptide binding in the allo-recognition. Furthermore, in the particular case of low expression of the recipient mismatched HLA-C antigen (MFI &lt; 115), CTLp reactivity depended on HLA-C expression level in the donor, the median MFI of donor’s mismatched HLA-C antigen was 114 in CTLp negative cases (<italic>n</italic> = 26), while in CTLp positive cases (<italic>n</italic> = 15) the median MFI of donor’s HLA-C antigen was 193 (<italic>p</italic> = 0.0093). We conclude that the expression level of the donor and recipient mismatched HLA-C antigens affect CTLp outcome. HLA-C antigen expression levels in combination with the CTLp assay may prove useful for the prediction of the clinical outcome of HLA-C mismatched HCT.</p>