This competitive renewal proposed to pursue studies on the human T cell antigen receptor (TCR) making use of a number of monoclonal antibodies (MAb) derived in our laboratory, which have specificity for shared variable region determinants of the TCR. Some of these MAb may be specific for certain V gene segments and thus serve as marker for V gene usage determined at the protein level. The individual projects are: 1) Determination of the epitopes recognized by the individual MAb and the gene segments which encode these epitopes. With these MAb we will further ask the question: Does V gene usage determine a bias for a particular MHC type? This will be assessed using derived T cell lines positive with the alpha TCR MAb and assaying alloreactivity patterns specific for the usage of a given V gene product. Also differences in expression of the TCR epitopes defined by the MAb will be analyzed as function of the HLA background of individuals to determine to what extent HLA type may influence TCR V gene usage. 2) A molecular basis for a MAb defined polymorphism of the human TCR will be sought. This has relevance because polymorphism of the human TCR may not be rare events and may be related to disease associations and Ag/MHC reactivity. These studies will involve cloning and sequencing of 2 alleles corresponding to an observed allelic polymorphism of a subset of TCRs, presumably a polymorphism of a V beta gene product. 3) An exciting new disease association between V beta 8 gene usage and Crohn's disease will be pursued in order to understand whether V beta 8 gene usage is genetically controlled and/or a result of a specific immune response linked to the disease process.
Showing the most recent 10 out of 21 publications
