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

Martin WD, Hicks GG, Mendiratta SK, Leva HI, Ruley HE, Van Kaer L
Cell. 1996 84 (4): 543-50

PMID: 8598041 · 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.

MeSH Terms (17)

Animals Antigen Presentation Antigens, Differentiation, B-Lymphocyte Biological Transport CD4-Positive T-Lymphocytes CD8-Positive T-Lymphocytes Gene Expression Histocompatibility Antigens Class II Lymphocyte Count Membrane Proteins Mice Mice, Mutant Strains Peptides Phenotype Protein Binding Spleen T-Lymphocytes

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