The human T-cell lymphotropic viruses (HTLV) are a family of exogenous, naturally occurring retroviruses which preferentially infect thymus-derived lymphocytes. HTLV type I is associated with adult T-cell leukemias and lymphomas worldwide, while HTLV type II was isolated from a patient with a T-cell variant of hairy cell leukemia. The purpose of this study is to characterize further an existing panel of monoclonal antibodies to HTLVI p19 core protein and associated glycoproteins for use as diagnostic probes and for the study of HTLVI host-viral interaction, and further to make a new panel of antibodies to HTLVII. Monoclonal anti-p19 antibodies which cross-react with HTLV uninfected normal host tissues will be screened for reactivity to a panel of 6 synthetic peptides encoded by the HTLVI p19 gag region gene, to identify amino acid sequences bearing cross-reactive antigenic sites. A panel of 9 HTLVI patient sera will be screened for reactivity to 6 p19 gag-encoded and 2 env-encoded synthetic peptides to identify viral antigens which are immunogenic in man. Eleven monoclonal antibodies to HTLVI-associated glycoproteins will be further characterized to assess whether they react with viral encoded envelope glycoproteins. HTLVI+ patient sera and antisera to env-encoded synthetic peptides will be used to characterize the reactivities of these antibodies to env-encoded products. Anti-glycoprotein antibodies will be screened for the ability to neutralize HTLVI infectivity in a syncytium inhibition assay and by co-culturing techniques. Antibodies which inhibit HTLVI infectivity will be used to raise anti-idiotype antibodies for use in the characterization of the HTLVI receptor on normal peripheral blood lymphocytes. Anti-glycoprotein antibodies will also be used as probes for the study of glycoprotein-cell receptor interaction. All antibodies to HTLVI proteins will be screened for reactivity to HTLVII to evaluate their ability to distinguish among HTLV types. In addition, monoclonal antibodies to HTLVII will be developed and characterized using techniques and expertise developed for production of monoclonal antibodies to HTLVI.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA040660-02
Application #
3548621
Study Section
(SRC)
Project Start
1985-07-01
Project End
1988-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Duke University
Department
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
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Hart, M K; Palker, T J; Haynes, B F (1995) Design of experimental synthetic peptide immunogens for prevention of HIV-1 and HTLV-I retroviral infections. Pharm Biotechnol 6:821-45
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Palker, T J; Tanner, M E; Scearce, R M et al. (1989) Mapping of immunogenic regions of human T cell leukemia virus type I (HTLV-I) gp46 and gp21 envelope glycoproteins with env-encoded synthetic peptides and a monoclonal antibody to gp46. J Immunol 142:971-8
Weinberg, J B; Spiegel, R A; Blazey, D L et al. (1988) Human T-cell lymphotropic virus I and adult T-cell leukemia: report of a cluster in North Carolina. Am J Med 85:51-8
Palker, T J; Clark, M E; Sarngadharan, M G et al. (1987) Purification of envelope glycoproteins of human T cell lymphotropic virus type I (HTLV-I) by affinity chromatography. J Virol Methods 18:243-55

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