Protective immunity against Plasmodium falciparum requires constant exposure to the pathogen. T cell-mediated immune responses are induced by T cell epitopes of pre-erythrocytic stage antigens of P. falciparum and involve HLA-restricted CD4 and CD8 cells. Cytotoxic T cell responses to a conserved epitope of P. falciparum liver stage antigen (LSA) type 1 are restricted by the HLA class I allele Bw53. The role of HLA class II alleles in mediating cellular responses against P. falciparum LSA-1 has not yet been demonstrated. In a longitudinal study performed for >4 years, associations were found between the HLA class II allele DQB1*0501 and protection from malaria anemia and malarial reinfections in Gabonese children. Children carrying DQB1*0501 had a higher frequency of interferon-gamma responses to LSA-1 T cell epitopes, compared with noncarriers.