Identification of talin head domain as an immunodominant epitope of the antiplatelet antibody response in patients with HIV-1-associated thrombocytopenia.
HIV-1-associated thrombocytopenia (HIV-1-ITP) is a common complication of HIV-1 infection, frequently caused by increased peripheral platelet destruction mediated by antiplatelet antibodies (Abs) and/or platelet-bound immune complexes. Little is known about the specificity of the antiplatelet Abs at a molecular level. Here, we used immunoglobulin G (IgG) phage-display libraries generated from 3 HIV-1-ITP patients to isolate a large panel of human monoclonal antiplatelet 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 that can be generated by platelet activation or HIV-1 protease. Talin-H was found in HIV-1-ITP-circulating immune complexes, and antitalin Abs were detected in HIV-1-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-1-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 immune complexes (ICs) may contribute to HIV-1-ITP.
Department of Immunology, The Scripps Research Institute, La Jolla, CA, USA.
Klaus
K
Koefoed
Henrik J
HJ
Ditzel
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000150:complications / Q000276:immunology*; D000595:Amino Acid Sequence; D000917:Antibody Formation; D001792:Blood Platelets / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D008969:Molecular Sequence Data; D012016:Reference Values; D016608:Talin / Q000737:chemistry / Q000276:immunology*; D013921:Thrombocytopenia / Q000209:etiology / Q000276:immunology*
D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D016608:Talin