SUBTYPES OF CLONED Ia - RESTRICTED HELPER T CELLS

Antihapten antibody responses to hapten-protein conjugates involve the collaborative interaction of hapten-speciflc B cells and carrier-specific helper T (Th) 1 cells (1). Our previous analysis of the B cell response to the hapten phosphorylcholine (PC) in vitro, using cloned, carrier-specific, Ia-restricted Th cells has shown the following: (a) The interaction of the cloned Th cell and a PC-specific B cell requires T cell recognition of B cell surface Ia glycoproteins; (b) the hapten PC must be physically linked to the protein carrier for which the Th are specific; (c) effective interaction between a cloned Th and a B cell is influenced by the quantity of B cell surface Ia glycoproteins; and, (d) many of the PC-specific B cells activated do not bear the prototype idiotypic determinant characteristic of the BALB/c PC-binding myeloma protein TEPC-15 (T15) (2). Studies evaluating the responses to PC-conjugated proteins have shown that intact in vivo responses as well as in vitro responses induced by uncloned Ly-1 T cells are dominated by T15-bearing B cells (3-5). This seems surprising given that there is idiotypic heterogeneity at the PC-specific precursor B cell level (6), this being convincingly documented recently by the finding (7) that only 48% of PC-specific precursors activated by lipopolysaccharide are T 15-bearing. Our own data have suggested that one can activate non-T15-bearing B cells in T-dependent responses using cloned Ia-restricted Th cells (2, 8, 9), and that an increase in the T15-bearing anti-PC response may require additional T cell signals (10, 11). Together, these findings suggest that the activation requirements of T 15-bearing and n o n T 15-bearing B cells may differ. We have now generated and characterized a series of cloned, antigen-specific, Ia-restricted T cell lines with different functional phenotypes. In this report, the characteristic four types of cloned Ia-restricted Th cells differ in their ability to activate T15-bearing and non-T15-bearing B cells. Further analysis of these functionally distinct cloned Th cells on individual PC-specific B ceils in limitingdilution experiments showed that these Th differed in their ability to activate