Constantin N . Baxevanis , Norihisa Ishii , Zoltan

Over the past few years, considerable progress has been made in the identification of regulatory T cell pathways and factors that act as mediators between T cell subsets involved in these pathways (1-3). However, at least two important aspects of regulation of the immune response have remained largely unexplored. One of them is the role of antigen presentation and of major histocompatibility complex (MHC)1 restriction in the activation of suppressor T (Ts) cells. From the paucity of reports on M H C restriction of Ts sets (4-8), one would conclude that MHC-restricted antigen presentation is not essential for the activation of most suppressor pathways. This view gains support from the demonstrated high affinity of some Ts cells for free antigen (9-11). It is, however, equally possible that the uncertainties about M H C restriction in Ts systems reflect the absence of an appropriate experimental model in which the interaction of Ts cells with antigen-presenting cells (APC) could be explored. The second aspect that appears to be neglected is the mechanism of interaction between Ts effector cells and their targets. The mode of action of suppressor-effector factors is largely unknown (12-14), and, to our knowledge, there is only one report in the literature that bears on the direct interaction between Ts cells and T helper (Th) cells (15). Our recent work on the proliferative T cell response to lactate dehydrogenase B (LDHB) has provided a system suitable to study the questions outlined above. We have demonstrated (6-18) that most H-2 haplotypes respond to LDHB and that the T cell proliferation in all responder haplotypes is restricted by the molecule controlled by the A~ and A~ loci in the I -A region of H 2 (A [A~Aa] molecules). The proliferating cells are most likely Th cells because their genetic control is almost identical with that of antibody production to LDHB (16, 19). Nonresponder haplotypes to LDHB include virtually all strains that carry the k allele at the E~ and E~ loci of the H 2 complex. However, nonresponsiveness can be reversed by in vivo or in vitro administration of monoclonal antibodies against the molecule controlled by the E~ locus in the I -A and * Supported in part by grant Wa 139/No/A.I5 from the Deutsche Forschungsgemeinschaft. 1 Abbreviations used in this paper: A molecule, controlled by the A~ and A• loci in the I-A region of H-2; APC, antigen-presenting cell; BudR, 5-bromo-2'-deoxyuridine; E molecule, controlled by the E B locus in the I-A and the E~ locus in the I-E region of H-2; GA, poly(Glue'°Ala4°) ; GAT, poly (Glu6°Alaa°Tyrl°); GT, poly (GluS°TyrS°); KLH, keyhole limpet hemocyanin; LDHB, lactate dehydrogenase B; MHC, major histocompatibility complex; SI, stimulation index; SRBC, sheep erythrocytes; Th, T helper cell; Ts, T suppressor cell; Tsel T suppressor effector; Tsi, T suppressor inducer.