LACK OF CORRELATION BETWEEN HLA CLASS-II ALLELES AND IMMUNE-RESPONSESTO PF155 RING-INFECTED ERYTHROCYTE SURFACE-ANTIGEN (RESA) FROM PLASMODIUM-FALCIPARUM IN MADAGASCAR

To investigate the relationships between predominant HLA class IT alle les and immune responses to the Plasmodium falciparum ring-infected er ythrocyte surface antigen (Pf155/RESA), 50 individuals from the highla nds of Madagascar were followed-up from 1988 to 1991. The T cell react ivity and antibody responses to synthetic peptides (EENV)(4), (EENVEHD A)(4), and (DDEHVEEPTVA)(3), representing major T and B epitopes of Pf 155/RESA antigen, were assessed with an average of five determinations per individual over the four-year follow-up period. The T cell reacti vity was investigated by lymphocyte proliferation and assays for inter feron-gamma and interleukin-2 release. Antipeptide antibodies were mea sured using the Falcon(R) assay screening test-enzyme-linked immunosor bent assay. The cumulative prevalence rates of cellular (range for the three peptides = 64-68%) and antibody responders (range = 70-74%) wer e similar for each peptide. The HLA class II typing was performed usin g polymerase chain reaction restriction fragment length polymorphisms. The prevalent alleles or groups of alleles (frequency > 20%) were sim ilar in responders and nonresponders, both for cellular and antibody r esponses to each peptide. These were HLA-DR 5 group and HLA-DQA1 0601 , 0101-0102-0104, HLA-DQB1 *0301, and HLA-DPB1 *0101-2601 alleles. Al lelic distribution was similar in individuals presenting with (74%) or without (26%) a malaria attack during a 20-week follow-up conducted w hen malaria was hyperendemic (P > 0.05, by Fisher's exact test). Despi te repeated immunelogic measures that better identify the responders, no relationship was found between HLA class II alleles and the cellula r or antibody responses to Pf155/RESA epitopes. If immune responses to Pf155/RESA epitopes or susceptibility to malaria attacks are genetica lly regulated, our data suggest the HLA class II region is not involve d.