The human leukocyte common antigen (LCA) consists of a family of at least five transmembrane glycoproteins whose differences in primary structure depend on alternative splicing of mRNA transcripts from a single gene. LCA expression by all leukocyte subsets and the existence of homologous LCA molecules among several animal species suggest an important, evolutionarily-conserved role in leukocyte biology which may be relevant to the entire spectrum of diseases involving leukocytes. More specifically, evidence exists that LCA proteins represent a set of cell surface receptors with protein tyrosine phosphatase activity that are involved in signal transduction and play a role in lymphoid proliferation, differentiation and cytotoxicity. This suggests that their study may enhance our understanding of cell proliferation and differentiation regulatory networks, and may prove to be clinically relevant to the management of infections, allergic and autoimmune disorders, allograft rejection, tumor-host interactions and tumor prevention. The detailed structural characterization of LCAs obtained from lymphoid subsets has been performed; however, there is little information available concerning LCA expression by immune-associated dendritic cells isolated from lymphoid tissue cell suspensions and peripheral blood. Recently, we have performed epitope mapping studies which strongly suggest that human Langerhans cells express a novel form of LCA. This raises the possibility that related mammalian dendritic cells may also express novel LCA isoforms. We propose to use two-color immunophenotyping, immunoprecipitation/SDS-PAGE, Northern blotting, PCR amplification, cDNA sequencing and S1 nuclease protection analysis to study the structure of LCA isoforms expressed by immune-associated dendritic cells in the human, mouse and rat. These studies will provide information concerning the relatedness of various immune-associated dendritic cells to one another and to other antigen-presenting cells such as monocytes/macrophages. This research will be the foundation for future efforts to raise anti-LCA monoclonal antibodies specific for dendritic cells, and to study the functional effects of cell transfection with different LCA cDNAs. This, in turn, will allow novel studies of immune- associated dendritic cell ontogeny/phylogeny and further our understanding of the functional significance of LCA isoform diversity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AR040844-02
Application #
3457522
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1991-04-01
Project End
1996-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Wood, G S; Uluer, A Z (1999) Polymerase chain reaction/denaturing gradient gel electrophoresis (PCR/DGGE): sensitivity, band pattern analysis, and methodologic optimization. Am J Dermatopathol 21:547-51
Wood, G S; Szwejbka, P; Schwandt, A (1998) Human Langerhans cells express a novel form of the leukocyte common antigen (CD45). J Invest Dermatol 111:668-73
Henghold 2nd, W B; Purvis, S F; Schaffer, J et al. (1997) No evidence of KSHV/HHV-8 in mycosis fungoides or associated disorders. J Invest Dermatol 108:920-2
Wood, G S; Schaffer, J M; Boni, R et al. (1997) No evidence of HTLV-I proviral integration in lymphoproliferative disorders associated with cutaneous T-cell lymphoma. Am J Pathol 150:667-73
Haeffner, A C; Zepter, K; Elmets, C A et al. (1997) Analysis of tumor-infiltrating lymphocytes in cutaneous squamous cell carcinoma. Arch Dermatol 133:585-90
Henghold 2nd, W B; Purvis, S F; Schaffer, J et al. (1997) Kaposi sarcoma-associated herpesvirus/human herpesvirus type 8 and Epstein-Barr virus in iatrogenic Kaposi sarcoma. Arch Dermatol 133:109-11
Khan, S G; Mohan, R R; Katiyar, S K et al. (1996) Mutations in ras oncogenes: rare events in ultraviolet B radiation-induced mouse skin tumorigenesis. Mol Carcinog 15:96-103
Wood, G S; Salvekar, A; Schaffer, J et al. (1996) Evidence against a role for human T-cell lymphotrophic virus type I (HTLV-I) in the pathogenesis of American cutaneous T-cell lymphoma. J Invest Dermatol 107:301-7
Wood, G S; Ruffo, A; Salvekar, A et al. (1996) Detection of human T-cell lymphotrophic virus type I in archival tissue specimens. Arch Dermatol 132:1339-43
Veelken, H; Sklar, J L; Wood, G S (1996) Detection of low-level tumor cells in allergic contact dermatitis induced by mechlorethamine in patients with mycosis fungoides. J Invest Dermatol 106:685-8

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