Effect of Carrier Modification on the Cellular and Serologic Responses of the Rat to the Tnp Hapten

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Abstract
Soluble trinitrophenylated keyhole limpet hemocyanin (s-TKLH) was made particulate by reacting with ethyl chloroformate. After i.p. injection, the anti-hapten response was measured by passive hemagglutination and by plaque-forming cells (PFC) in the parathymic lymph nodes (PLN) and spleen. Titers were higher, and the slopes of the log phase were dose-independent for particulate TKLH; titers were lower, and the slopes of the log phase were dose-dependent for soluble TKLH. The peak number of 7S PFC in the PLN was sustained with particulate TKLH, but decreased rapidly with soluble TKLH. The number of PFC in the spleen was not above background. The priming ability of particulate antigen was 10 to 100 times that of soluble antigen in the PLN, other lymph nodes and spleen. Particulate TKLH was phagocytosed by macrophages 20 to 30 times more efficiently than was soluble TKLH. Association with macrophages, however, enhanced the immunogenicity of soluble TKLH greatly, while it almost abolished the primary response to particulate TKLH, and significantly reduced the secondary response. Furthermore, antigen-containing granulomata found in the peritoneal cavity 3 days after injection of the particulate antigen did not induce an immune response when transplanted to normal rats. We concluded that increased uptake or differential processing by peritoneal macrophages does not account for the greater immunogenicity of particulate TKLH. Retention of particulate TKLH in the liver and spleen was much greater than that of soluble TKLH, and may account for some, but not all, of the differences we report. Possible suppressive effects of excess soluble antigen will be discussed in a subsequent paper.

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