In our recombinant screening program during the past year, we have picked up a very important recombinant. This recombinant mouse seems to have a crossing over within the H-2D region. The parental mice were of the H-2?b? and H-2?d? haplotypes. The recombinant has markers of D?d? and L?b? genes of the two parents. This suggests a gene order of D, L, R, and is the first such recombination in this region. In the past year, we produced several alloreactive clones that express Ia antigens. These clones grow without any external stimulation and have helped to solve the controversy that T cells do synthesize Ia antigens rather than taking them up from the macrophages. During the past year, we picked up five putative Ia mutants in our screening program and are analyzing them. We found that prolongation of allograft survival mediated by cyclosporin is not effective in certain MHC haplotypes, suggesting the in vivo metabolism of cyclosporin may be influenced by some MHC gene product. We are further analyzing this effect. We made considerable progress on the heterogeneity of Ia molecules. A few years ago we reported that there were more Ia polypeptides than were known at that time using monoclonal antibodies. Molecular biologists at that time claimed only isolation of four Ia genes, which made our results look doubtful. In the past six months, new Ia A?beta? and E?beta? genes have been identified, thus confirming our results on the biochemical identification of multiple Ia molecules. We are in the process of doing two-dimensional gel analysis and peptide mapping to confirm our results. (CS)

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Immunobiology Study Section (IMB)
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Mayo Clinic, Rochester
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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
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
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
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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