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Chapter 8,752

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

Martin, W.D.; Hicks, G.G.; Mendiratta, S.K.; Leva, H.I.; Ruley, H.E.; Van Kaer, L.

Cell 84(4): 543-550

1996


ISSN/ISBN: 0092-8674
PMID: 8598041
DOI: 10.1016/s0092-8674(00)81030-2
Accession: 008751241

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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