title: H-2M3a violates the paradigm for major histocompatibility complex class I peptide binding.
abstract: The major histocompatibility (MHC) class I-b molecule H-2M3a binds and presents N-formylated peptides to cytotoxic T lymphocytes. This requirement potentially places severe constraints on the number of peptides that M3a can present to the immune system. Consistent with this idea, the M3a-Ld MHC class I chimera is expressed at very low levels on the cell surface, but can be induced significantly by the addition of specific peptides at 27 degrees C. Using this assay, we show that M3a binds many very short N-formyl peptides, including N-formyl chemotactic peptides and canonical octapeptides. This observation is in sharp contrast to the paradigmatic size range of peptides of 8-10 amino acids binding to most class I-a molecules and the class I-b molecule Qa-2. Stabilization by fMLF-benzyl amide could be detected at peptide concentrations as low as 100 nM. While N-formyl peptides as short as two amino acids in length stabilized expression of M3a-Ld, increasing the length of these peptides added to the stability of peptide-MHC complexes as determined by 27-37 degrees C temperature shift experiments. We propose that relaxation of the length rule may represent a compensatory adaptation to maximize the number of peptides that can be presented by H-2M3a.
authors.affiliation: Department of Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Vyas
authors.forename: J R
authors.initials: JR
authors.lastname: Rodgers
authors.forename: R R
authors.initials: RR
authors.lastname: Rich
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D006183:H-2 Antigens / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009245:NADH Dehydrogenase / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*
chemical_list: D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D009245:NADH Dehydrogenase