T-lymphocyte activation by immunogenic determinants.
Synthetic antigens have been of great value in elucidating the relationships between antigen structure and lymphocyte activation. The compound RAT behaves as a monofunctional antigen in guinea pigs and mice, inducing T-lymphocyte responses without appreciable circulating antibody, although the ABA-specific B cell population is expanded by immunization with the monovalent molecule. On the other hand, bifunctional antigens composed of one RAT moiety serving as a carrier and a second chemical group, either identical to or different from RAT, serving as a hapten, induced antibody responses. In such responses, T cell specificity was always directed against the RAT component. Using symmetrical bifunctional antigens with rigid or flexible spacers between the two determinants, marked differences in structural requirements for cell triggering, assessed by antigen-induced lymphocyte proliferation, and for cell cooperation, determined by antibody formation, were found. Rigidly spaced bifunctional antigens serve admirably for cooperation but poorly for T cell activation, underscoring the advantage of two-point binding for the latter.