HLA-DRB1 allelic combinations differentially shape dendritic cell antigen presentation enhanced by tumor cell line lysate-pulsing

The study explores the anti-tumor immune response through the analysis of the HLA-II immunopeptidome of dendritic cells (DCs) from HLA-heterozygous donors pulsed with a protein extract from the MCF-7 tumor cell line. The objective was to characterize how different HLA-DRB1 allele combinations influence peptide presentation and how DC pulsing affects the immunopeptidome profile. Our findings demonstrate that HLA-DR heterozygosity significantly shapes the peptide repertoire in an allele-specific manner, with allele dominance modulated by specific allelic combinations. Notably, tumor-derived peptides such as annexin A2, galectin-1, and elongation factor 1-alpha 2 were identified in association with particular HLA-DRB1 alleles. These insights provide valuable information for the design of personalized immunotherapies based on peptide-pulsed DCs aimed at enhancing CD4+ tumor-infiltrating lymphocyte responses.