Identification of Bphs, an autoimmune disease locus, as histamine receptor H1

Bphs controls Bordetella pertussis toxin (PTX) induced vasoactive amine sensitization elicited by histamine (VAASH) and has an established role in autoimmunity. We report that congenic mapping links Bphs to the histamine H-1 receptor gene (Hrh1/H1R) and that H1R differs at three amino acid residues in VAASH-susceptible and -resistant mice. Hrh1(-/-) mice are protected from VAASH, which can be restored by genetic complementation with a susceptible Bphs/Hrh1 allele, and experimental allergic encephalomyelitis and autoimmune orchitis due to immune deviation. Thus, natural alleles of Hrh1 control both the autoimmune T cell and vascular responses regulated by histamine after PTX sensitization.