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. 1997 Oct;65(10):4190–4198. doi: 10.1128/iai.65.10.4190-4198.1997

Allelic polymorphisms at the H-2A and HLA-DQ loci influence the response of murine lymphocytes to the Mycoplasma arthritidis superantigen MAM.

B C Cole 1, A D Sawitzke 1, E A Ahmed 1, C L Atkin 1, C S David 1
PMCID: PMC175602  PMID: 9317026

Abstract

Mycoplasma arthritidis, an agent of rodent arthritis, produces a potent superantigen (SAg), MAM. Previous work established that MAM is presented to T cells by murine H-2E or the homologous human HLA-DR molecules and that lymphocytes lacking a functional H-2E molecule fail to respond to MAM. Recently, more potent and purified preparations of MAM of known protein content have become available. This enabled us to more effectively compare the response of MAM with that of other SAgs by using lymphocytes from mice whose cells express different H-2A and HLA-DQ molecules. Here we demonstrate that cells from some H-2E-negative mouse strains respond to higher concentrations of MAM. By use of inbred, congenic, 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 MAM. In addition, polymorphisms at HLA-DQ, the human homolog of H-2A, also influence responsiveness to MAM. Cells expressing DQw6 (HLA-DQA1*0103 and DQBI*0601 chains) gave much higher responses to MAM than did cells expressing DQw8 (DQA1*0301 and DQB1*0302 chains). In fact, responses of lymphocytes expressing DQB1*0601 chains homozygously were as high as those observed for cells expressing a functional H-2E molecule. Murine lymphocytes responded less well to staphylococcal enterotoxin B (SEB) and SEA, but mouse cells expressing human MHC molecules gave much higher responses. The patterns of reactivity observed with cells expressing the various murine and human alleles differed for MAM, SEB, and SEA, suggesting that each of these SAgs interacts with different regions or residues on MHC molecules. It has been hypothesized that SAgs might play a role in susceptibility to autoimmune disease. Allelic polymorphisms at MHC loci might therefore influence susceptibility to autoimmune disease by affecting immunoreactivity to specific superantigens.

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Selected References

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