期刊
JOURNAL OF IMMUNOLOGY
卷 180, 期 3, 页码 1619-1633出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.180.3.1619
关键词
-
类别
资金
- NHLBI NIH HHS [T32 HL066988-10, T32 HL066988, T32 HL 66988] Funding Source: Medline
- NIAID NIH HHS [AI I 19047, T32 AI007285, R21 AI059898, R21 AI059898-01, R21 AI 059898, R01 AI051542, R01 AI 51542, R37 AI019047-18, T32 AI 007285, R01 AI051542-01] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
The MHC-encoded cofactor DM catalyzes endosomal loading of peptides onto MHC class II molecules. Despite evidence from in vitro experiments that DM acts to selectively edit the repertoire of class II:peptide complexes, the consequence of DM expression in vivo, or a predictive pattern of DM activity in the specificity of CD4 T cell responses has remained unresolved. Therefore, to characterize DM function in vivo we used wild-type (WT) or DM-deficient (DM-/-) mice of the H-2(d) MHC haplotype and tested the hypothesis that DM promotes narrowing of the repertoire of class II:peptide complexes displayed by APC, leading to a correspondingly selective CD4 T cell response. Surprisingly, our results indicated that DM-/- mice do not exhibit a broadened CD4 T cell response relative to WT mice, but rather shift their immunodominance pattern to new peptides, a pattern associated with a change in class II isotype-restriction. Specifically, we found that CD4 T cell responses in WT mice were primarily restricted to the I-A class II molecule, whereas DM-/- mice recognize peptides in the context of I-E. The observed shift in isotype-restriction appeared to be due in part to a modification in the peripheral CD4 T cell repertoire available for peptide recognition.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据