LBOR03: ASSOCIATION BETWEEN CTL PRECURSOR FREQUENCY TO HLA-C MISMATCHES AND HLA-C ANTIGEN CELL SURFACE EXPRESSION

Abstract

Aim Previous studies showed the relevance of the cytotoxic T cell precursor frequency assay (CTLp) 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. Methods In total 115 recipient–donor pairs, for whom a successful CTLp assay was performed, were evaluated in 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 MFI values as described by Apps et al. (Science, 2013). Results The cell surface expression of recipient’s mismatched C antigen was significantly lower among CTLp negative ( n = 59) compared to CTLp positive ( n = 56) pairs (154 and 193 MFI units, respectively; p = 0.0031). This difference was more pronounced in donor–recipient pairs that were mismatched for residue-116 located in the groove of the HLA-C antigen, suggesting the importance of peptide binding in the allo-recognition. Furthermore, in the case of low expression of the recipient mismatched HLA-C antigen (MFI n = 26), while in CTLp positive cases ( n = 15) the median MFI of donor’s HLA-C antigen was 193. ( P = 0.0093). Conclusion 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.