PfCSP epitopes are presented on HLA alleles with variable prevalence. (A) IL-2 concentrations as measured by ELISA in supernatants of TCR-transgenic CD4⁺ Jurkat76 T cells co-cultured with autologous B cells pulsed with the indicated peptides in the presence (+) or absence (−) of the indicated locus-specific HLA-blocking antibodies. (B) IL-2 concentrations as measured by ELISA in supernatant of TCR-transgenic CD4⁺ Jurkat76 T cells co-cultured with peptide-pulsed autologous (aut.) or heterologous (het.) B cells that share one (+) or no (−) locus-specific HLA allele with the respective autologous B cells. Epitope-presenting HLA alleles were determined (activation observed in co-cultures with heterologous B cells expressing a single share allele) or inferred (lack of activation in heterologous B cells with one shared allele) and are highlighted in gray. (C) HLA alleles presenting the indicated PfCSP epitopes in the 15 donors described in this study (DRB1*13:02, DRB1*04:03, DQB1*06:03, DRB1*10:01, and DQB1*02:02) or previously (DRB1*07:01 and DRB1*15:01 [Wahl et al., 2022b]). Gray shading indicates the presence of an allele. Black frames indicate epitope-specific CD4⁺ T cell responses as determined in A. (D) Frequency of donors with HLA alleles shown to present the indicated epitopes. (A and B)n indicates the number of tested T cell lines. One out of two independent experiments is shown.