[HTML][HTML] H2-M mutant mice are defective in the peptide loading of class II molecules, antigen presentation, and T cell repertoire selection

WD Martin, GG Hicks, SK Mendiratta, HI Leva… - Cell, 1996 - cell.com
WD Martin, GG Hicks, SK Mendiratta, HI Leva, HE Ruley, L Van Kaer
Cell, 1996cell.com
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 …
Abstract
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.
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