HLA-DRB1 等位基因组合差异性塑造由肿瘤细胞系裂解物脉冲增强的树突状细胞抗原呈递

The anti-tumour immune response plays a pivotal role in eliminating tumour cells, with the presence of tumour-infiltrating lymphocytes (TILs) often correlated with improved patient outcomes. Among these, CD4+ T lymphocytes act as key orchestrators of the immune response, functioning as effector and regulatory cells, and are essential for establishing immunological memory.

To better understand the role of CD4+ T cells in anti-tumour immunity, we analysed the HLA-II immunopeptidome of dendritic cells (DCs) from HLA-heterozygous donors pulsed with a protein extract from the MCF-7 tumour cell line.

Our objective was to identify differences in the arrays of peptides binding distinct HLA-DRB1 allele combinations and the effect of DC pulsing on peptide presentation.

We found that presented peptide repertoires are strongly influenced by HLA-DR heterozygosity in an allele-specific manner. Alleles with high binding strength (e. g. , DRB1*01:01, DRB1*03:01 and DRB1*04:04) tended to dominate peptide presentation; however, this dominance is significantly modulated by the allelic combination, suggesting that antigen presentation is shaped not only by individual allele properties but also by their combinations.

Pulsing DCs with MCF-7 extracts increased peptide overlap between donors and enabled the identification of 58 proteins putatively derived from the tumour cell line lysates. Interestingly, peptide presentation from these proteins reinforced allele-specific features of dominance and weakness previously observed across the entire immunopeptidome.

Gaining insights into the peptide repertoire presented by distinct HLA-DR combinations could inform the design of personalised immunotherapies based on peptide-pulsed DCs, ultimately enhancing CD4+ TIL responses across diverse patient populations.