In vitro analysis of allogeneic lymphocyte interaction. VI. I-J-restricted self-reactive and alloreactive components of allogeneic effect factor (AEF) are distinct I-J- molecules that interact with I-J+ T cells and antigen-presenting cells.

An allogeneic effect factor (AEF) generated across an I-J incompatibility was derived from MLR cultures of alloactivated B10.A(3R) responder T cells and irradiated T cell-depleted B10.A(5R) stimulator spleen cells. This AEF consists of two soluble, secreted I-J-restricted helper components. One helper component, TH-I, recognizes self-I-J determinants on an I-J+ B10.A(3R) antigen-presenting cell (APC), whereas the other helper component, TH-II, recognizes allo-I-J determinants on an I-J+ B10.A(5R) APC. TH-I-B10.A(3R) APC interaction and TH-II-B10.A(5R) APC interaction each induce an in vitro primary anti-SRBC PFC response of either B10.A(3R) or B10.A(5R) B cells. Thus, I-J determinants serve as restricting elements during a TH-APC and not an APC-B interaction. TH-II mediates the I-J-restricted allogeneic effect required to activate T suppressor (TS) cells during a contact sensitivity or delayed-type hypersensitivity response to hapten-conjugated syngeneic lymphoid cells. This indicates that TH-II is also involved in a TH-pre-TS type interaction. TH-I and TH-II are I-J-, 68,000 m.w. molecules that differ by about 0.10 units in their pl values. Their charge difference is not due to an altered amount of sialylation or phosphorylation, but may result either from another form of altered glycosylation and/or from a difference in their primary structure. Peptide mapping analyses reveal that TH-I and TH-II possess at least 80% shared peptides and may be structurally homologous but nonidentical molecules; however, the possibility that TH-I and TH-II are structurally identical cannot be eliminated. Papain cleaves TH-I and TH-II into a 40,000 m.w. fragment. No subunit structure of TH-I and TH-II is apparent. It is suggested that TH-I and TH-II are I-J- -activated responder T cell-derived receptors for self-I-J and allo-I-J determinants, respectively.