Major histocompatibility complex-restricted and unrestricted T helper cells recognizing minor histocompatibility antigens of B cell surfaces.

The present experiments analyze the functional properties of helper T cells specific for "minor" histocompatibility antigens. T cells from C3H/HeJ mice, primed in vivo and highly enriched in vitro for reactivity to membrane antigens of C3H/Tif B cells, specifically proliferate, and provide polyclonal help to splenic B cells from strains carving a variety of different H-2 haplotypes on C3H or BALB backgrounds, while failing to respond to cells carrying the same H-2 haplotypes on C57BL or A backgrounds. Since it has been previously demonstrated (A.A. Augustin and A. Coutinho, J. Exp. Med. 1980. 151: 587) and B cell activation in this system strictly requires direct, specific recognition of B cell surface antigens by helper cells and does not result from the production of soluble "mitogenic" or "nonspecific helper factors", it is concluded that this phenomenon represents specific, major histocompatibility complex (MHC)-unrestricted T cell help. In addition, it has now been found that expression of helper activity requires viability of the helper cells and is partially radiation-sensitive. Lack of MHC restriction is not a general property of specific helper cells which directly recognize B cell "minor" antigens, since BALB.C3H anti-C3H/Tif T cells appear to be restricted by H-2 in their polyclonal helper activity. The helper activity mediated by specific anti-"minor", H-2 restricted helper cells could not be inhibited by anti-VH antibodies, and the inhibition obtained with anti-Ia antibodies appeared to operate at the level of B cell induction, rather than at the level of helper cell activation.