T cell immunobiology of alloimmune thrombocytopenias.
Allorecognition and generation of alloantisera depend on T cell help. Here we summarize our recent work on identifying the T cells that recognize a specific platelet alloantigen generated by a Pro to Leu polymorphism in beta-chain of the platelet integrin alphaIIb beta3. The ability to generate alloantibodies is restricted by HLA-DRB3*0101. By measuring peptide binding to HLA-DRB3*0101, we have shown that the polymorphism controls the generation of the T cell epitope. This is not a result of the polymorphism changing a T cell contact residue, but rather by its generating a peptide anchor. The result is a directional antibody response in which only the beta-chain that is antigenic is the one that produces a peptide that binds to the HLA-DR. This mechanism of generating alloantibodies may be a paradigm for a whole class of responses.
Gorski
J
J
Blood Research Institute, Blood Center of Southeastern Wisconsin, Milwaukee 53201-2178, USA.
Yassai
M
M
Wu
S
S
Maślanka
K
K
D000818:Animals; D001792:Blood Platelets / Q000276:immunology; D006801:Humans; D007519:Isoantigens / Q000276:immunology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics / Q000276:immunology*; D011110:Polymorphism, Genetic; D013601:T-Lymphocytes / Q000276:immunology*; D013921:Thrombocytopenia / Q000097:blood / Q000276:immunology*
D007519:Isoantigens; D019039:Platelet Glycoprotein GPIIb-IIIa Complex