Immunological mimicry between host and microbial proteins has been sug
gested as a potential mechanism in the development of uveitis in human
s. In this study immunological corssreactivity between anti-streptococ
cal monoclonal antibodies (MAbs) and the human eye was investigated. I
n indirect immunofluorescence, we demonstrated novel immunological cro
ssreactivity of two antistreptococcal MAbs (27 and 112) with the rod o
uter (and inner) segments of the retina of the human eye. In further s
tudies, retinal S-Ag, a uveitogenic protein in the rod outer (and inne
r) segments, was found to react with the anti-streptococcal MAbs. In a
ddition, several uveitogenic peptides of S-Ag were recognized by the a
nti-streptococcal MAbs. In the ELISA and Western immunoblot, anti-S-Ag
MAbs crossreacted with group A streptococci and the streptococcal M p
rotein Further demonstrating sites of antigenic similarity. Homology b
etween the retinal S-Ag and streptococcal M protein was observed in am
ino acid sequences repeated in the B repeat region of the streptococca
l M5 protein. These data show that retinal S-antigen has immunological
similarities with streptococcal M protein, a major virulence determin
ant and strong bacterial cell surface antigen.