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

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.

MeSH terms

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


  • Antigens, Differentiation, B-Lymphocyte
  • Histocompatibility Antigens Class II
  • Membrane Proteins
  • Peptides
  • invariant chain