Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MHC class II heterozygotes form haplotype-mismatched heterodimers (combining alpha and beta chains of different alleles). Transfected L-cells expressing Aalpha(d)Abeta(d) or Aalpha(d)Abeta(b) presented exogenous OVA(323-339) peptide to T cells with similar high efficiency, while Aalpha(b)Abeta(b) was less efficient and Aalpha(b)Abeta(d) was ineffective. In contrast, Aalpha(d)Abeta(b) greatly exceeded Aalpha(d)Abeta(d) in processing of intact OVA for presentation of OVA(323-339); Aalpha(b)Abeta(b) was even less efficient and Aalpha(b)Abeta(d) was ineffective. Of macrophages from C57BL/6 (H-2(b)), DBA/2 (H-2(d)) and B6D2F1 (H-2(bxd))mice, B6D2F1 macrophages had highest I-A expression and efficiency for OVA processing or presentation of exogenous OVA(323-339) peptide. Blocking antibodies specific for I-A chains showed that OVA processing by B6D2F1 macrophages primarily involved haplotype-mismatched Aalpha(d)Abeta(b) heterodimers, whereas Aalpha(d)Abeta(d) and Aalpha(b)Abeta(b) contributed more to presentation of exogenous OVA(323-339) peptide. OVA(323-339):I-A complexes were formed from OVA within 10 min with B6D2F1 macrophages but not until 20 min with C57BL/6 or DBA/2 macrophages, and OVA processing was more resistant to inhibition of late endocytic function by hypothermia (18 degrees C) in B6D2F1 than C57BL/6 or DBA/2 macrophages. These results indicate that Aalpha(d)Abeta(b) haplotype-mismatched heterodimers may contribute to antigen processing in early endocytic compartments.
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PMID:Differences in antigen processing with haplotype-mismatched MHC class II heterodimers: Aalpha(d)Abeta(b) heterodimers participate in early endosomal processing. 1235 24

Staphylococcal enterotoxins (SEs) belong to a large group of bacterial exotoxins that cause severe immunopathologies, especially when delivered as an aerosol. SEs elicit the release of lethal amounts of cytokines by binding to major histocompatibility complex (MHC) class II and cross-linking susceptible T-cell receptors. Efforts to develop effective therapeutic strategies to protect against SEs delivered as an aerosol have been hampered by the lack of small animal models that consistently emulate human responses to these toxins. Here, we report that human leukocyte antigen-DQ8 (HLA-DQ8) transgenic (Tg) mice, but not littermate controls, succumbed to lethal shock induced by SEB aerosols without potentiation. Substantial amounts of perivascular edema and inflammatory infiltrates were noted in the lungs of Tg mice, similar to the pathology observed in nonhuman primates exposed by aerosol to SEB. Furthermore, the observed pathologies and lethal shock correlated with an upsurge in proinflammatory cytokine mRNA gene expression in the lungs and spleens, as well as with marked increases in the levels of proinflammatory circulating cytokines in the Tg mice. Unlike the case for littermate controls, telemetric evaluation showed significant hypothermia in Tg mice exposed to lethal doses of SEB. Taken together, these results show that this murine model will allow for the examination of therapeutics and vaccines developed specifically against SEB aerosol exposure and possibly other bacterial superantigens in the context of human MHC class II receptors.
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PMID:Human leukocyte antigen-DQ8 transgenic mice: a model to examine the toxicity of aerosolized staphylococcal enterotoxin B. 1578 91