Abstract

and Specific Aims.): This study will analyze class II structure/function in vivo by producing and analyzing mutant class II transgenic (tg) mouse strains.
Specific Aim 1 proposes to generate appropriate tg mice to examine the role of A beta mutations on antigen presentation, the T-cell repertoire, and on autoimmunity.
Specific Aim 2 will examine class II interaction with CD4 by mutating the presumptive CD4 binding site of A beta genes and generating appropriate tg mice.
Specific Aim 3 will analyze class II sites involved in dimer-dimer formation in vitro in transfected L cells and in vivo in tg mice. This will be approached by introducing mutations at sites believed to be involved in dimer-dimer formation.
Specific Aim 4 will focus on generating soluble class II A and E molecules for tolerance studies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA024473-18
Application #
2700331
Study Section
Immunobiology Study Section (IMB)
Program Officer
Mccarthy, Susan A
Project Start
1978-04-01
Project End
2000-04-30
Budget Start
1998-05-01
Budget End
2000-04-30
Support Year
18
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905

  Publications

Finn, Thomas P; Jones, Richard E; Rich, Cathleen et al. (2004) HLA-DRB1*1501 risk association in multiple sclerosis may not be related to presentation of myelin epitopes. J Neurosci Res 78:100-14
Huber, S A; Sakkinen, P; David, C et al. (2001) T helper-cell phenotype regulates atherosclerosis in mice under conditions of mild hypercholesterolemia. Circulation 103:2610-6
Abraham, R S; David, C S (2000) Identification of HLA-class-II-restricted epitopes of autoantigens in transgenic mice. Curr Opin Immunol 12:122-9
Krco, C J; Harders, J; Chapoval, S et al. (2000) Immune response of HLA-DQ transgenic mice to house dust mite allergen p2: identification of HLA-DQ restricted minimal epitopes and critical residues. Clin Immunol 97:154-61
Das, P; Drescher, K M; Geluk, A et al. (2000) Complementation between specific HLA-DR and HLA-DQ genes in transgenic mice determines susceptibility to experimental autoimmune encephalomyelitis. Hum Immunol 61:279-89
Papouchado, B G; Chapoval, S P; Marietta, E V et al. (2000) HLA-DQ/human CD4-restricted immune response to cockroach allergens in transgenic mice. Tissue Antigens 55:303-11
Pan, S; Taneja, V; Griffiths, M M et al. (1999) Complementation between HLA-DR4 (DRB1*0401) and specific H2-A molecule in transgenic mice leads to collagen-induced arthritis. Hum Immunol 60:816-25
Huber, S A; Stone, J E; Wagner Jr, D H et al. (1999) gamma delta+ T cells regulate major histocompatibility complex class II(IA and IE)-dependent susceptibility to coxsackievirus B3-induced autoimmune myocarditis. J Virol 73:5630-6
Pan, S; Trejo, T; Hansen, J et al. (1998) HLA-DR4 (DRB1*0401) transgenic mice expressing an altered CD4-binding site: specificity and magnitude of DR4-restricted T cell response. J Immunol 161:2925-9
Lomo, L C; Zhang, F; McCormick, D J et al. (1998) Flexibility of the thyroiditogenic T cell repertoire for murine autoimmune thyroiditis in CD8-deficient (beta2m -/-) and T cell receptor Vbeta(c) congenic mice. Autoimmunity 27:127-33

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