Structural similarities between host self-antigens and infectious organisms may be involved in the expression of autoimmune reactivity and development of autoimmune disease. The unique eye pathology associated with Onchocerca volvulus infection, particularly the development of posterior segment lesions, may be promoted by such autoreactive responses. Ov39 is a parasite-derived antigen that has been shown previously to be antigenically cross-reactive with a 44,000-M(r) host ocular component. A clone, designated hr44, was isolated from a cDNA library of human retina by immunoscreen using serum to Ov39. A monoclonal antibody raised to Ov39 also reacted with hr44 and gave evidence for a shared conformational epitope. The primary structure analysis showed that identities between the antigens are limited and confined to small peptides. The cross-reactivity between the antigens appears to involve T cells, since Ov39-specific T cells can be stimulated by hr44, a neural-specific antigen. Based on secondary structure prediction, hr44 has the typical features of a membrane-associated type I antigen with an amino-terminal extracellular domain. mAbs and antisera localized the antigen in the optic nerve, neural retina, retinal pigment epithelium, as well as the epithelial layers of ciliary body and iris.