Molecular mimicry: histone H3 and mycobacterial protein epitopes

A 15-kDa protein detected initially in amyloidotic ileum from a transgenic mouse and subsequently in control (nontransgenic) ileum by various polyclonal rabbit antiserums applied to electroblots of extracts derived from these tissues was identified by partial sequence analysis as histone H3. Antiserums were made against immunogens unrelated to the histone, but they recognized calf thymus histone H3 (14.7 kDa) on Western blots. The bacterial component of the Freund's medium used as an adjuvant for the immunogens was either Mycobacterium butyricum or Mycobacterium smegmatis. Absorption tests with histone H3 and sonicated M. butyricum substantiated the presence of anti-histone H3 activity in the antiserums. These findings indicate that the two mycobacterium species make a protein with epitopes perceived as nonself by recipient rabbits but sufficiently similar to epitopes of mammalian histone H3 that the rabbits produced antibodies cross-reactive with the histone.