It is now well established that T cells play an essential role in the initiation and regulation of antibody responses. The T cells which participate in B cell antibody responses appear to be heterogeneous, complex mixtures of interacting cells which both promote and suppress B cell responses. Consequently, the precise analysis of the specificity of functional helper T cells depends on developing means of analyzing individual T cells in collaboration with B cell populations. We propose to employ two experimental approaches to study individual helper T cells. The first is a limiting dilution analysis which we have successfully employed in this laboratory to analyze antigen-specific helper T cells in collaboration with nonimmune primary B cells. This approach has the advantage of allowing a determination of the frequency and specificity of a helper T cell within an individual T cell repertoire. The second approach we will employ is the establishment of long term cloned helper T cell lines. Although it is difficult to draw general conclusions concerning the T cell repertoire in vivo from cloned T cell lines, this approach offers the enormous advantage of providing a large homogeneous population of T cells for analysis. Used in conjunction, these two protocols are a very powerful tool for the study of the helper T cell repertoire. Employing these two techniques, we will focus our attention on three aspects of the recognition potential of helper T lymphocytes. These are: 1) the T cells' fine specificity for foreign antigenic determinants, 2) the T cell repertoire's recognition of antigen in the context of MHC encoded molecules, and 3) the T cells recognition of antibody. It is hoped that these studies will lead to a better understanding of the precise nature of the T cells' recognition of antigen and B cell surface gene products and the functional potential of the T cells to promote B-cell responses through this recognition.
Showing the most recent 10 out of 48 publications
