The activation of helper T cells specific for soluble globular protein antigens requires the processing of the native antigen to a peptide fragment and the subsequent presentation of the peptide on the surface of an Ia expressing cell. Recent evidence indicates that B cells are capable of functioning as antigen presenting cells and that the Ig receptor plays a role in this process by binding and internalizing the native antigen for subsequent processing and presentation and/or by augmenting the B cell's antigen presentation properties by an as yet undefined mechanism. These findings are important because they provide a mechanism by which processing and presentation can be carried out in an antigen specific fashion, and by which the helper T cells can be directed to the antigen-specific B cell surface where they are activated and subsequently release b cell stimulating factors. This proposal represents an approach to the study of the mechanism of B cell antigen processing and presentation and of the role of the surface Ig in this function. The experiments proposed will use cytochrome c as antigen because it is a protein of well defined spatial structure for which the antigenic determinants recognized by an antibodies and the peptide fragment which constitutes the T cell antigen have been identified. Using the array of naturally occurring variant cytochromes c as well as their chemically modified derivatives and a set of corresponding synthetic peptides containing the T cell antigenic determinant, three questions will be addressed: (1) What is the role of the surface Ig in B cell antigen presentation? (2) By what mechanism is the antigenic peptide held on the B cell surface? and (3) In what subcellular organelle is the native protein cleaved to release the antigenic peptide? It is hoped that these studies will allow for a description at the molecular level of antigen processing and of the role of the B cel surface Ig in regulating or enhancing this process.
