Studying malaria-infected mice, we have shown for the first time that expression of T cells bearing specific V-beta T cell receptor elements can influence the outcome of an infectious disease process. Inbred strains of mice can differ markedly in their ability to resist infection with lethal or nonlethal isolates of the malaria parasite Plasmodium yoelii. We have shown that MHC genes and genes mapping outside the MHC, as well as parasite genetic factors influence the outcome of these infections. Our studies have now demonstrated that expression in the host of an endogenous mouse mammary tumor virus (MTV-7), originally described as the product of the Mis-1a gene, can alter the host's ability to resist P. yoelii infection. Because endogenous mouse mammary tumor viruses such as MTV-7 encode superantigens that react with and then effect the deletion (or anergy) of T cells bearing specific V-beta TCR elements, we conducted studies to confirm that mice that have been specifically depleted of T cells bearing relevant V-beta TCR elements are resistant to infection when compared to mice possessing such cells. Our data demonstrate that it may not be possible to predict the success of vaccination trials, or the outcome of malaria infections without prior knowledge of the host's exposure to superantigens expressed by an array of other infectious or endogenous agents. To characterize the host immune responses that are regulated by the relevant TCR-bearing cells in malaria-infected mice, we will study the humoral and cellular immune responses of MTV-7(Mis-1) congenic mouse strains, and mouse strains which express human HLA DQ transgenes known to mediate deletion of specific V-beta TCR-bearing T cells. Responses of mice specifically depleted of certain V-beta TCR- bearing cells by injection of either V-beta-specific monoclonal antibodies or Mis disparate cells will also be characterized. Our data suggest that any factor that alters the T cell repertoire, either before or after birth, could potentially alter the host's ability to resist malaria or other infectious diseases.
