ALLELIC POLYMORPHISMS AT THE H-2A AND HLA-DQ LOCI INFLUENCE THE RESPONSE OF MURINE LYMPHOCYTES TO THE MYCOPLASMA-ARTHRITIDIS SUPERANTIGEN MAM

Mycoplasma arthritidis, an agent of rodent arthritis, produces a poten t superantigen (SAg), MAM, Previous work established that MAM is prese nted to T cells by murine H-2E or the homologous human HLA-DR molecule s and that lymphocytes lacking a functional H-2E molecule fail to resp ond to MAM, Recently, more potent and purified preparations of MAM of known protein content have become available, This enabled us to more e ffectively compare the response of MAM with that of other SAgs by usin g lymphocytes from mice whose cells express different H-2A and HLA-DQ molecules, Here we demonstrate that cells from some H-2E-negative mous e strains respond to higher concentrations of MAM. By use of inbred, c ongenic, and recombinant mice, we show that these differences are, in fact, exercised at the level of the major histocompatibility complex ( MHC) and that allelic polymorphisms at H-2A influence reactivity to MA M. In addition, polymorphisms at HLA-DQ, the human homolog of H-2A, al so influence responsiveness to MAM. Cells expressing DQw6 (HLA-DQA101 03 and DQB10601 chains) gave much higher responses to MAM than did ce lls expressing DQw8 (DQA10301 and DQB1*0302 chains), In bet, response s of lymphocytes expressing BQB10601 chains homozygously were as high as those observed for cells expressing a functional H-2E molecule, Mu rine lymphocytes responded less well to staphylococcal enterotoxin B ( SEE) and SEA, but mouse cells expressing human MHC molecules gave much higher responses, The patterns of reactivity observed with cells expr essing the various murine and human alleles differed for MAM, SEE, and SEA, suggesting that each of these SAgs interacts with different regi ons or residues on MHC molecules, It has been hypothesized that SAgs m ight play a role in susceptibility to autoimmune disease, Allelic poly morphisms at MHC loci might therefore influence susceptibility to auto immune disease by affecting immunoreactivity to specific superantigens .