This proposal is based on the hypothesis that there exists a relationship between the expression of certain T-cell functions and the context in which a T-cell recognizes particular MHC molecules. The following aims are included in the studies proposed herein: 1. Investigation of the functional, genetic restriction and antigen specificity profiles of TLC's directed at influenza viral hemagglutinin determinants but restricted by different interaction products encoded within HLA-D subregions such as HLA-DR, DQ and DP. 2. Elucidation of the nature and extent of class II molecules expressed by human T-cells and the role of these molecules in regulating direct communication between functional T- cells. 3. Investigation of the genetic components of the HLA-D region using alloreactive T-lymphocyte clones. The antigen specificity of human T-cell clones will be closely defined with synthetic peptides corresponding to the influenza hemagglutinin molecule. The genetic restriction of these clones will be grossly defined in panel studies and in family segregation analyses; restriction fine specificity will be probed using monoclonal antibodies specific for D-region class II molecules. The data will be examined for correlations between T-cell specificity and function as an approach to understanding the genetic control of human immune responsiveness. The significance of this proposal is based on the need to develop in vitro models of human immunoregulation; it should contribute information useful to areas such as basic human genetics, transplantation biology and immune pathology. Potential conceptual applications exist with respect to allergy, anergic states (e.g., deficient responses to parasitic organisms in schistosomiasis and leprosy) and autoimmunity. In all of these areas, the determinant structures on disease-related antigens and their perhaps subtle interactions with HLA-encoded, class II restriction elements are poorly understood and need explanation.
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