The goal of this project is to evaluate the requirements for the processing of integral membrane protein antigens prior to presentation to T cells of the helper-inducer phenotype (T?h?). Although it has been demonstrated that several and perhaps all soluble protein antigens require internalization, partial degradation and re-expression of """"""""processed"""""""" antigen on the accessory cell surface before recognition by T?h? cells, it is not known if antigens such as MHC class I and class II transplantation antigens or viral envelope glycoproteins which are expressed as integral membrane proteins on antigen presenting cells require processing before presentation to T?h? cells. As an initial model to test the requirements for processing of integral membrane proteins we would specifically like to study the envelope glycoproteins of herpes simplex virus (HSV) which, because of the availability of various HSV mutants, will allow us to study the processing requirements using the same glycoproteins when presented as an integral membrane protein versus an isolated soluble protein. In the coming year we will: (1) prepare T cells and T-cell hybridomas that have been sensitized to, and are specific for, HSV envelope glycoproteins. Sensitization will be performed using intact virus as well as purified soluble glycoprotein antigen obtained from HSV mutants; (2) determine if antigen processing is required for the presentation of HSV expressed as an integral membrane protein compared to a soluble protein antigen; and (3) in conjunction with the studies proposed in specific aim 1 we will compare the capacity of B cells and B cell tumors with macrophages for their ability to present integral membrane antigens to T?h? cells. The elucidation of the requirements for presentation of integral membrane viral antigens to T?h? cells will provide important insight into the requirements for the activator of T?h? cells necessary for the induction of immune responses against viral antigens as well as transplantation antigens as well as viral antigens. (CS)
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