Many proteins that serve recognition functions outside the nervous system belong to the same family of structurally-related molecules, the HIBIT (HLA, Ia, b2-microglobulin, immunoglobulin, Thy-1) superfamily. Genetic studies show that still othe gene products of this family remain to be identified. Although this family has primarily been studied in lymphoid tissue, it is not limited to lymphoid tissue: Thy-1 is a major cell surface protein of neurons. We hypothesize that: (1) Some """"""""new"""""""" HIBIT proteins are in the nervous system, and (2) like the other members of this family, they serve recognition functions. We will exploit techniques I have used previously, to reveal new HIBIT proteins in neural tissue. We will use monoclonal antibodies (MoAbs) to known HIBIT proteins to look for new variants. We will also raise MoAbs to cross-reactive intra-family determinants, to be used as more general probes for new HIBIT proteins. In general terms, our work will show how MoAbs may be used as probes for multi-gene families, particularly when conventional isolation and biochemical characterization of the molecules are difficult. This would apply to proteins present in small quantities, or cell types that cannot be separated, and must therefore be compared in microscopic assays. Our previous work illustrates the clinical relevance of this work: We have found weak HLA-A,B,C expression on human cells of neuronal origin, which has implications concerning the growth potential of neuronal tumors, and neural transplants. In later studies, we will determine the nature of possible polymorphisms (cell to cell, tissue to tissue, etc.) of new HIBIT proteins; this will suggest the type of recognition function each might serve.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS024878-03
Application #
3409859
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1986-07-01
Project End
1992-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115
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Sethna, M P; Lampson, L A (1991) Immune modulation within the brain: recruitment of inflammatory cells and increased major histocompatibility antigen expression following intracerebral injection of interferon-gamma. J Neuroimmunol 34:121-32
Lampson, L A; Kushner, P D; Sobel, R A (1990) Major histocompatibility complex antigen expression in the affected tissues in amyotrophic lateral sclerosis. Ann Neurol 28:365-72
Wen, P; Loeffler, J S; Morris, J H et al. (1990) The effects of irradiation on major histocompatibility complex expression and lymphocytic infiltration in the normal rat brain and the 9L gliosarcoma brain tumor model. J Neuroimmunol 27:239-44
Turner, W J; Chatten, J; Lampson, L A (1990) Human neuroblastoma cell growth in xenogeneic hosts: comparison of T cell-deficient and NK-deficient hosts, and subcutaneous or intravenous injection routes. J Neurooncol 8:121-32
Kassis, A I; Van den Abbeele, A D; Wen, P Y et al. (1990) Specific uptake of the auger electron-emitting thymidine analogue 5-[123I/125I]iodo-2'-deoxyuridine in rat brain tumors: diagnostic and therapeutic implications in humans. Cancer Res 50:5199-203
Lampson, L A (1990) MHC regulation in neural cells. Distribution of peripheral and internal beta 2-microglobulin and class I molecules in human neuroblastoma cell lines. J Immunol 144:512-20