We propose to elucidate the role of B lymphocytes in the amplification of the immune response to bacterial antigens and to study the biology and immunogenetics of T cell recognition and response to such antigens. For these experiments we have developed a battery of reagents which are necessary for studies of interactions between antigen specific T cell clones, monocytes and B lymphocytes in humans. These reagents include: tetanus specific T cell clones, Epstein Barr virus transformed B cell lines from a panel of alloantibodies and monoclonal antibodies against HLA-D region gene products and antiidiotypic antisera to human tetanus toxoid antibodies. The experiments proposed will focus on: 1) the study of MHC (Ia-like) restriction of monocyte and EBV-B lymphoblast interactions with antigen specific T cell clones, 2) the study of the immunobiology of the T cell recognition unit for Ia associated antigen i.e. whether the T cell receptor involves independent recognition of baterial antigen and Ia determinants versus recognition of self Ia altered by antigen. 3) The study of antigen presentation by activated B lylmphocytes and 4) the possible activation of B lymphocytes by the T cell recognition unit or specific helper factors. Monoclonal antibodies directed against 3 different kinds of Ia-like molecules will be used to extend observations which indicate that one kind of Ia determinants are more important in the antigen presentation than other Ia like antibodies. These findings could have long term relevance in future attempts to selectively inhibit alloreactivity leaving intact recognition of environmental antigens. Such discoveries could be applicable in future designs of treatments for autoimmune diseases and in allotransplantation. The basic significance of this work to immunology in general is to define the biological role of activated B lymphocytes in the amplification of immune responses to bacterial antigens.
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