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Blood, 15 December 2004, Vol. 104, No. 13, pp. 4054-4062.
Prepublished online as a Blood First Edition Paper on August 17, 2004; DOI 10.1182/blood-2004-01-0386.


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Submitted February 4, 2004
Accepted July 28, 2004

Identification of talin head domain as an immunodominant epitope of the anti-platelet antibody response in patients with HIV-1-associated thrombocytopenia

Klaus Koefoed and Henrik J Ditzel*

Department of Immunology, The Scripps Research Institute, La Jolla, CA, USA
Department of Immunology, The Scripps Research Institute, La Jolla, CA, USA; The Medical Biotechnology Center, Institute of Medical Biology, University of Southern Denmark, Odense, Denmark; Department of Internal Medicine C, Odense University Hospital, Odense, Denmark

* Corresponding author; email: hditzel{at}health.sdu.dk.

HIV-1-associated thrombocytopenia (HIV-1-ITP) is a common complication of HIV-1 infection, frequently caused by increased peripheral platelet destruction mediated by anti-platelet antibodies (Ab) and/or platelet-bound immune complexes. Little is known about the specificity of the anti-platelet Abs at a molecular level. Here, we used IgG phage display libraries generated from three HIV-1-ITP patients to isolate a large panel of human monoclonal anti-platelet Abs by selection on unfixed platelets. The platelet antigen recognized by all the cloned Abs was identified to be the talin head domain (talin-H), a cleavage product of talin, which can be generated by platelet activation or HIV-1 protease. Talin-H was found in HIV-1-ITP circulating immune complexes, and anti-talin Abs were detected in HIV-ITP sera, but not in controls. The cloned anti-talin-H IgGs were highly somatically-mutated, indicative of an antigen-driven, affinity-matured response. These findings suggest that talin-H Ab may be a marker of HIV-ITP elicited due to exposure of immunodominant epitopes on talin-H as a result of a disease-related process. Abs to talin-H and related ICs may contribute to HIV-1-ITP.


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