Several inbred mouse strains were screened for their ability to respond to the ordered periodic collagen-like polymer (Pro-Gly-Pro)n, to the random copolymer (Pro66, Gly34)n, to the protein conjugate Pro-Gly-Pro-ovalbumin, to rat tail tendon collagen, rat tail tendon gelatin, and to Ascaris cuticle collagen. Differences were obtained in the magnitude of the antibody titers towards the above immunogens among the strains tested. The level of the response to the ordered polymer (Pro-Gly-Pro)n was not similar to that towards the random (Pro66, Gly34)n, confirming differences in the antigenic determinants of the two immunogens.
The role of the thymus in the immune response to (Pro-Gly-Pro)n and (Pro66, Gly34)n as well as to two collagens and gelatin, was studied in order to find out a possible correlation with the structural features of the immunogens. Heavily irradiated recipients were injected with syngeneic thymocytes, marrow cells, or a mixture of both cell populations and were immunized with the above-mentioned antigens. An efficient immune response to the ordered collagen-like (Pro-Gly-Pro)n was obtained in the absence of transferred thymocytes. The thymus independence of (Pro-Gly-Pro)n was confirmed when thymectomized irradiated mice were used as recipients. In contrast with these results, cooperation between thymus and marrow cells was necessary in order to elicit an immune response to (Pro56, Gly34)n. Similarly, the immune response to the triple helical collagen was found to be independent of the thymus, whereas for an effective response to its denatured product, gelatin, thymus cells were required. These findings indicate that a unique three-dimensional structure of immunogens possessing repeating antigenic determinants plays an important role in determining the need for cell to cell interaction in order to elicit an antibody response.