Martin W D, Hicks G G, Mendiratta S K, Leva H I, Ruley H E, Van Kaer L
Howard Hughes Medical Institute, Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Cell. 1996 Feb 23;84(4):543-50. doi: 10.1016/s0092-8674(00)81030-2.
H2-M is a nonconventional major histocompatibility complex (MHC) class II molecule that has been implicated in the loading of peptides onto conventional class II molecules. We generated mice with a targeted mutation in the H2-Ma gene, which encodes a subunit for H2-M. Although the mutant mice express normal class II cell surface levels, these are structurally distinct from the compact SDS-resistant complexes expressed by wild-type cells and are predominantly bound by class II-associated invariant chain peptides (CLIPs). Cells from these animals are unable to present intact protein antigens to class II-restricted T cells and show reduced capacity to present exogenous peptides. Numbers of mature CD4+ T lymphocytes in mutant mice are reduced 3- to 4-fold and exhibit altered reactivities. Overall, this phenotype establishes an important role for H2-M in regulating MHC class II function in vivo and supports the notion that self-peptides contribute to the specificity of T cell positive selection.
H2-M是一种非常规的主要组织相容性复合体（MHC）II类分子，它与将肽装载到常规II类分子上有关。我们构建了在编码H2-M一个亚基的H2-Ma基因中有靶向突变的小鼠。尽管突变小鼠表达正常水平的II类细胞表面分子，但这些分子在结构上与野生型细胞表达的紧密抗SDS复合物不同，并且主要与II类相关恒定链肽（CLIP）结合。来自这些动物的细胞无法将完整的蛋白质抗原呈递给II类限制性T细胞，并且呈现外源性肽的能力降低。突变小鼠中成熟CD4+ T淋巴细胞的数量减少了3至4倍，并且反应性发生改变。总体而言，这种表型确立了H2-M在体内调节MHC II类功能中的重要作用，并支持自身肽有助于T细胞阳性选择特异性的观点。
