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

Barry C. Cole, Allen D. Sawitzke, Elsayed A. Ahmed, Curtis L. Atkin, Chella S. David

Research output: Contribution to journalArticle

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Abstract

Mycoplasma arthritidis, an agent of rodent arthritis, produces a potent super antigen (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 DQB1*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.

Original languageEnglish (US)
Pages (from-to)4190-4198
Number of pages9
JournalInfection and Immunity
Volume65
Issue number10
StatePublished - Oct 1997

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Mycoplasma arthritidis
HLA-DQ Antigens
Lymphocytes
Major Histocompatibility Complex
Autoimmune Diseases
Congenic Mice
Superantigens
HLA-DR Antigens
Mycoplasma arthritidis mitogen
Arthritis
Rodentia
Alleles
T-Lymphocytes
Antigens

ASJC Scopus subject areas

  • Immunology

Cite this

Allelic polymorphisms at the H-2A and HLA-DQ loci influence the response of murine lymphocytes to the Mycoplasma arthritidis superantigen MAM. / Cole, Barry C.; Sawitzke, Allen D.; Ahmed, Elsayed A.; Atkin, Curtis L.; David, Chella S.

In: Infection and Immunity, Vol. 65, No. 10, 10.1997, p. 4190-4198.

Research output: Contribution to journalArticle

Cole, Barry C. ; Sawitzke, Allen D. ; Ahmed, Elsayed A. ; Atkin, Curtis L. ; David, Chella S. / Allelic polymorphisms at the H-2A and HLA-DQ loci influence the response of murine lymphocytes to the Mycoplasma arthritidis superantigen MAM. In: Infection and Immunity. 1997 ; Vol. 65, No. 10. pp. 4190-4198.
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abstract = "Mycoplasma arthritidis, an agent of rodent arthritis, produces a potent super antigen (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 DQB1*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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