Melanins are associated with virulence in several important human path
ogens, but little is known about the immune response to this ubiquitou
s biologic compound. We hypothesized that melanin produced by the fung
us Cryptococcus neoformans was immunogenic. C, neoformans melanin was
purified from melanized fungal cells and was used to immunize C57BL/6,
BALB/c, and T cell-deficient (nude) BALB/c mice. The Ab response was
evaluated by ELISA, immunofluorescence, and agglutination, The results
demonstrate that melanin can be immunogenic, and the humoral immune r
esponse is T cell independent. Furthermore, the experiments demonstrat
e 1) a sensitive ELISA for the measurement of Ab to melanin, 2) that m
ice mount an intense Ab response to fungal melanin that includes Abs o
f IgM and IgG isotypes, 3) that melanins from different sources have c
ross-reactive epitopes, and 4) melanin in the cell wall of melanized y
east cells reacts with Abs raised to L-dopa C, neoformans melanin. The
biologic significance of Ab to melanin remains to be determined, but
the development of Ab suggests that this amorphous insoluble polymer c
an stimulate the immune system. The serologic techniques described her
e may prove useful for the evaluation of Ab responses to melanin in a
variety of diseases.