Assessing the binding of four Plasmodium falciparum T helper cell epitopesto HLA-DQ and induction of T-cell responses in HLA-DQ transgenic mice

A subunit vaccine for Plasmodium falciparum malaria will need to contain we ll-defined T helper cell epitopes that induce protective immune responses t o the parasite. One major barrier to the use of subunit vaccines is the req uirement for T helper cell epitopes to be presented by the HLA class II mol ecules that are present in the population being vaccinated. Since the major ity of malaria studies have focused on HLA-DR, little information on the ro le of HLA-DQ in the binding and immune response to malarial epitopes is ava ilable. This study used an in vitro peptide-binding assay to predict the ex tent of HLA-DO binding of four conserved T helper cell epitopes identified from asexual-stage malaria vaccine candidate antigens, Epstein-Barr virus ( EBV)-transformed human B-cell lines expressing 14 different DQ molecules (D Q2.1, -2.2, -4.1, -4.2, -5.1 to -5.3, -6.1, -6.2, -6.4, -7.1, -7.3, -8, and -9) representing all broad serological specificities, including common DQ molecules present in populations in areas where malaria is endemic, were us ed in the binding assay. Moreover, an HLA-DQ transgenic mouse model was emp loyed to evaluate the correlation between the in vitro DQ binding of the pe ptides and the generation of in vivo immune responses following peptide imm unization. This study identified two broad DO-binding peptides, ABRA#14 and SERA#9. ABRA#14 also induced T-cell proliferation and Th1-associated cytok ine production in DQ8(+) transgenic mice. The combination of peptide bindin g to EBV-transformed cell lines and DQ transgenic mice provides a method fo r identifying additional T-cell epitopes for inclusion in a vaccine.