T cell clones specific for IgG2a of the a allotype: Direct evidence for presentation of endogenous antigen

T cell clones specific for IgG2a of the a allotype have been isolated from C57BL/6J mice. Antigenic determinants recognized by these clones were localized by using a panel of hybrid IgG2b-IgG2a myeloma proteins. These experiments provide evidence for two distinct antigenic sites, one located in a segment encompassing the hinge region and most of the C(H)2 domain, and the other in a segment spanning the C(H)3 domain and the C-terminal eight residues of the C(H)2 domain. As judged by their failure to respond in the presence of B6.C-H-2(bm12) spleen cells, all the clones recognize determinants created, in part, by the I-A(β) chain. A strong proliferative response was observed in the presence of spleen cells from several H-2^b strains, including C3H.SW, A.BY, D1.LP, and BALB.B. Experiments testing reactivity directed toward spleen cells from appropriate allotype-congenic mouse strains demonstrated that this response was controlled by Igh-linked genes. These results clearly indicated 1) that Igh-1a-specific T cell clones are stimulated by endogenously synthesized IgG2a, and 2) these T cells recognize shared determinants expressed on IgG2a molecules of various strains. These experiments thus provide strong evidence for presentation of self antigens under normal physiological conditions.