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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Modified Research Career Development Award (K04)
Project #
5K04AI000799-03
Application #
3070844
Study Section
Immunobiology Study Section (IMB)
Project Start
1987-07-01
Project End
1992-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Bloodcenter of Wisconsin, Inc.
Department
Type
DUNS #
City
Milwaukee
State
WI
Country
United States
Zip Code
53233
Kawaguchi, M; Eckels, D D (1995) Differential activation through the TCR-CD3 complex affects the requirement for costimulation of human T cells. Hum Immunol 43:136-48
Garlie, N K; Eckels, D D (1994) Idiotype-specific autologous T-cell interactions restricted by HLA-DR. Hum Immunol 39:69-75
Hurley, C K; Steiner, N; Wagner, A et al. (1993) Nonrandom T cell receptor usage in the allorecognition of HLA-DR1 microvariation. J Immunol 150:1314-24
Newton-Nash, D K; Eckels, D D (1993) Differential effect of polymorphism at HLA-DR1 beta-chain positions 85 and 86 on binding and recognition of DR1-restricted antigenic peptides. J Immunol 150:1813-21
Newton-Nash, D K; Eckels, D D (1992) Effects of localized HLA class II beta chain polymorphism on binding of antigenic peptide and stimulation of T cells. Hum Immunol 33:213-23
Oshima, S; Eckels, D D (1990) Selective signal transduction through the CD3 or CD2 complex is required for class II MHC expression by human T cells. J Immunol 145:4018-25
Oshima, S; Eckels, D D (1990) Selective expression of class II MHC isotypes by MLC-activated human T lymphocytes. Hum Immunol 27:208-19
Eckels, D D; Geiger, M J; Sell, T W et al. (1990) Involvement of class II beta-chain amino acid residues 85 and 86 in T-cell allorecognition. Hum Immunol 27:240-53
Sell, T W; Eckels, D D (1990) Primary mixed lymphocyte responses to HLA-DP. Hum Immunol 29:23-30
Sell, T W; Eckels, D D (1989) T-cell identification of a private DQw5 subtype associated with DR1: contribution of endogenous peptide? Hum Immunol 24:219-28

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