This research proposal is concerned with studies of the major histocompatibility complex in inbred and wild Norway rat populations. The major emphasis of the experimental work will focus on three areas of investigation. The first is a continued examination of the genetic fine structure of the MHC of the wild rat, attempting to demonstrate; (a) the genetic and serological characteristics of the histocompatibility (Ag-B) antigens found in the wild, particularly the number of loci that control their expression, (b) whether deficiencies in specific complement components, e.g., Ss proteins, can be identified in the rat and to establish such strains in the laboratory, and (c) the genetic control of the MLR and its complexities in the wild rat population. The second area is the development of antisera capable of recognizing the number and distribution of Ia-like antigens expressed on lymphocytes of wild and inbred animals. We are primarily interested in determining whether or not antisera produced in inbred strains are capable of recognizing the same antigenic structures in wild rat populations and what is their relationship to the MLR and the immune responsiveness to simple antigens. The third major aspect of this proposal will be to utilize the antisera directed against Ia-like specificities in an attempt to determine if they can specifically inhibit the MLR and/or Ir response in vitro. The effect of the antisera will be tested in both inbred and wild animals with specific genotypes and the inhibitory capacity of the sera will be compared to the degree of cytotoxicity against the appropriate strains of rats. The ability to detect specific components of the MHC in individual wild rats provides the opportunity to use natural genetic recombinations within the MHC as a rich source of genetic variation within the MHC. Characterization of individual wild animals and comparison to standard inbred strains will allow us to establish genetically useful recombinants as specific lines and to test the effects of various components of the MHC on several important immunological functions controlled by the complex.