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Med Hypotheses. 2001 Nov;57(5):583-90.

An immune hypothesis of sexual orientation.

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Sexual orientation is encoded within immune-cell subsets (ICS) of mucosal and epithelial tissues. Gender orientation may be encoded within other ICS. Many immune cells: recognize and react to H-Y and H-X antigens; and enact these perceptions and reactions in accord with the perceiver's and the perceived's MHC haplotype, XX or XY status, and immune-self recognition. Non-heterosexual orientations derive from excessive cross-priming, accompanied by clonal deletions, clonal expansions, anergy and tolerance. For at least some tissues, cross-priming sufficient to induce altered orientations may occur during critical periods of immunological development and can occur during fetal and infant development via maternal-fetal transfusion, placental pathology, and impaired maternal nutrient-status or via excessive peripheral apoptosis during postnatal illness. Mast cell interactions with neurons illustrate how mucosal perceptions can be transduced into neuronal signals that modulate CNS events. This hypothesis is testable by mixed-lymphocyte reactions in appropriate cell subsets. Dendritic-cell immunizations are a potential therapy.

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