In the present study, we demonstrate delayed-type hypersensitivity (DTH) to homologous type I collagen that cross-reacts with type IV collagen. Mice immunized with native or denatured type I collagens and challenged with these same antigens or native type IV collagen develop a peak DTH response on day 7. Challenge with denatured type IV collagen or collagenase-treated type IV collagen failed to elicit DTH in type I collagen-sensitized mice. Type I collagen-sensitized spleen cells adoptively transferred DTH to types IV and I collagen to normal recipients; T cell-depleted spleen cells failed to transfer immunity. Periodate-treated type IV collagen did not elicit DTH in mice sensitized to type I collagen; however, mice sensitized with type IV collagen displayed significant DTH when challenged with periodate-treated type IV collagen. Furthermore, treatment of type IV collagen with a mixed glycosidase or alpha-glucosidase before challenge eliminated the DTH response in type I collagen-sensitized mice; beta-galactosidase treatment of type IV collagen had no effect on this response. Mice sensitized with type IV collagen, however, displayed significant DTH when challenged with these glycosidase-treated antigens. Antibodies produced to types I and IV collagen by repeated immunizations were specific for the sensitizing antigen and did not react with other connective tissue antigens. These studies indicate that a CMI response to type I collagen recognizes similar antigenic determinants on the type IV collagen molecule. These cross-reacting determinants are dependent on conformation and contain carbohydrates, particularly glucose residues.

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