Immune recognition of a molecule naturally presented as a monomeric or an oligomeric structure: the model of the human chorionic gonadotropin alpha subunit.
The immune recognition of a molecule naturally presented as a monomeric or an oligomeric structure is analyzed using the human chorionic gonadotropin alpha subunit (hCG-alpha) as a model. Indeed, hCG-alpha circulates as either a free subunit or combined to the beta subunit (hCG-beta) to form the dimeric hCG hormone. A T cell study was performed in BALB/c (H-2d) mice which were found to be high responders to hCG-alpha. Mice were immunized with the free hCG-alpha or the dimeric hCG alpha/beta, and their lymph node cells were challenged in vitro with either alpha subunits from different species, hCG or peptides spanning the entire primary structure of hCG-alpha. Proliferation and IL-2 assays demonstrated that hCG-alpha-primed lymph node cells responded equally well to hCG-alpha and hCG alpha/beta, suggesting that both the free and combined hCG-alpha subunits are processed in a similar way. Among the various synthetic peptides used, only those mimicking the hCG-alpha(59-92) C-terminus portion were able to stimulate hCG-alpha-primed lymph node cells, demonstrating that this region contains immunodominant T cell recognition site(s). The hCG-alpha(23-43) and (32-59) peptides, although incapable of stimulating T cells primed with hCG-alpha, elicited a T cell response when used as immunogens. These regions encompassed cryptic epitopes which were not generated during hCG-alpha processing in H-2d mice. The T cell epitopes of hCG-alpha above described as immunodominant or cryptic on the free alpha subunit, had similar characteristics when the alpha/beta dimer was used as the immunogen. In contrast, T cells primed with peptides mimicking immunodominant sites recognized differently the hCG-alpha and the hCG alpha/beta antigens. Moreover, the analysis of the B cell response to all the immunogenic hCG-alpha peptides indicated that they bear B and T cell epitopes as well. Antibodies elicited against the hCG-alpha(59-92) or (32-59) peptide were capable of recognizing the alpha subunit in its free form but not in the alpha/beta hCG dimer. Such study deserves attention for the comprehensive mechanisms of the immune response to hCG as well as for the design of anti-hCG vaccines.
Rouas
N
N
Laboratoire d'Immunologie, Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes, CNRS, Paris, France.
Christophe
S
S
Bellet
D
D
Troalen
F
F
Guillet
J G
JG
Bidart
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology; D006063:Chorionic Gonadotropin / Q000737:chemistry / Q000276:immunology*; D000939:Epitopes; D015292:Glycoprotein Hormones, alpha Subunit / Q000737:chemistry / Q000276:immunology*; D006736:Horses; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D016415:Sequence Alignment; D012756:Sheep; D013601:T-Lymphocytes / Q000276:immunology
D006063:Chorionic Gonadotropin; D000939:Epitopes; D015292:Glycoprotein Hormones, alpha Subunit; D007376:Interleukin-2; D046911:Macromolecular Substances; D010455:Peptides