QUANTIFICATION OF THE RELATIVE CONTRIBUTION OF MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) AND NON-MHC GENES TO HUMAN IMMUNE-RESPONSES TO FOREIGN ANTIGENS

Understanding the extent to which genetic factors influence the immune response is important in the development of subunit vaccines. Associa tions with HLA gene polymorphisms appear insufficient to explain the r ange of variation in immune responses to vaccines and to infections by major pathogens. In this study of Gambian twins we report that regula tion of the immune response to a variety of antigens from Plasmodium f alciparum and Mycobacterium tuberculosis is controlled by factors whic h are encoded by genes that lie both within and outside the major hist ocompatibility complex (MHC). We define the relative contribution of t hese genes, which varies for different antigens. The cumulative geneti c contribution of non-MHC genes to the total phenotypic variance excee ds that of the MHC encoded genes.