Wednesday, May 16, 2012
Interaction of the humoral immune system with peptides presented by class I major histocompatibility (MHC) complexes [B Lymphocyte Signaling and Transcription]
Antibodies usually bind to unprocessed antigens, while cytotoxic T cells react with peptides derived from intracellular antigens when presented by class I major histocompatibility (MHC) complexes. We screened human sera for antibodies reacting specifically with the influenza matrix protein (IMP) derived peptide (58-66) displayed by HLA-A*0201 complexes by ELISA. Among blood donors, high-titered HLA-A*0201/IMP (58-66) complex-specific IgG antibodies were detected in HLA-A*0201- females with a history of pregnancies. Extended analyses of specificity indicated that these antibodies interacted peptide-specific with the MHC complex. No antibodies were detected in HLA-A*0201+ female or male blood donors. In another cohort of 218 females on delivery, only HLA-A*0201- mothers had HLA-A*0201/IMP (58-66) antibodies, which were also detected in the cord blood of the newborns, demonstrating that HLA-A*0201/ IMP58-66 antibodies are produced in HLA-A*0201- mothers and enter the fetal blood system. Refolding the peptide IMP (58-66) with all HLA-A, -B and -Cw alleles of the mothers and newborns revealed, that these antibodies are allo-reactive and are binding in some cases to the peptide displayed by a MHC allele of an offspring. Therefore allo-MHC/IMP (58-66) antibodies might provide immunity in HLA-disparate pregnancies. These antibody responses specific to a peptide displayed by a class I MHC complex opens a new dimension of interactions between the cellular and humoral immune system (read more).
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