Abstract

In man multiple B cell alloantigenic systems encoded by the HLA-D region of the major histocompatibility complex have been defined. These are often referred to as Ia antigens. Recombinant DNA studies suggest that as many as six distinct Ia loci exist, although biochemical and genetic studies have only formally demonstrated the expression of three of them. The molecules encoded by the Ia loci display a high degree of polymorphism due to multiple amino acid sequence differences among allotypes. This polymorphism is manifested functionally in that different allotypes determine differences in immune responsiveness. In addition many diseases that display autoimmune characteristics such as rheumatoid arthritis and multiple sclerosis are associated with particular Ia allotypes. We wish to analyze the molecular basis of variability among Ia molecules using biochemical and recombinant DNA techniques. More specifically we wish to ask the following questions: How many different Ia molecules can a single individual express? What are the molecular relationships of different Ia molecules within the same individual? What are the molecular relationships of Ia molecules between individuals? We believe these studies will help us to understand how Ia molecules regulate immune responsiveness and determine disease susceptibility.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI022005-02
Application #
3132584
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1984-07-01
Project End
1989-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Hospital for Joint Diseases Ortho Institute
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10003

  Publications

Zhou, Zhifeng; Lin, Xing-Yu; Akolkar, Pradip N et al. (2002) Variation at NOD2/CARD15 in familial and sporadic cases of Crohn's disease in the Ashkenazi Jewish population. Am J Gastroenterol 97:3095-101
Akolkar, P N; Gulwani-Akolkar, B; Lin, X Y et al. (2001) The IBD1 locus for susceptibility to Crohn's disease has a greater impact in Ashkenazi Jews with early onset disease. Am J Gastroenterol 96:1127-32
Gulwani-Akolkar, B; Akolkar, P N; Lin, X Y et al. (2000) HLA class II alleles associated with susceptibility and resistance to Crohn's disease in the Jewish population. Inflamm Bowel Dis 6:71-6
Heresbach, D; Gulwani-Akolkar, B; Lesser, M et al. (1998) Anticipation in Crohn's disease may be influenced by gender and ethnicity of the transmitting parent. Am J Gastroenterol 93:2368-72
Akolkar, P N; Gulwani-Akolkar, B; Heresbach, D et al. (1997) Differences in risk of Crohn's disease in offspring of mothers and fathers with inflammatory bowel disease. Am J Gastroenterol 92:2241-4
Gulwani-Akolkar, B; Akolkar, P N; Minassian, A et al. (1996) Selective expansion of specific T cell receptors in the inflamed colon of Crohn's disease. J Clin Invest 98:1344-54
Gulwani-Akolkar, B; Akolkar, P N; Minassian, A et al. (1996) CD4+ cell oligoclonality in Crohn's disease: evidence for an antigen-specific response. Hum Immunol 48:114-24
Akolkar, P N; Chirmule, N; Gulwani-Akolkar, B et al. (1995) V beta-specific activation of T cells by the HIV glycoprotein gp 160. Scand J Immunol 41:487-98
Silver, J; Gulwani-Akolkar, B; Akolkar, P N (1995) The influence of genetics, environment, and disease state on the human T-cell receptor repertoire. Ann N Y Acad Sci 756:28-52
Akolkar, P N; Gulwani-Akolkar, B; Silver, J (1995) Differential patterns of T-cell receptor BV-specific activation of T cells by gp120 from different HIV strains. Scand J Immunol 42:598-606

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