Distinguishing self from nonself: immunogenicity of the murine H47 locus is determined by a single amino acid substitution in an unusual peptide.

Document Type

Article

Publication Date

2001

Keywords

Amino-Acid-Sequence, Autoantigens, Cell-Line, Isoleucine, Membrane-Proteins, Mice-Inbred-BALB-C, Mice-Inbred-C57BL, Minor-Histocompatibility-Antigens, Molecular-Sequence-Data, Mutagenesis-Site-Directed, Oligopeptides, Peptide-Fragments, Phenylalanine, Polymorphism-(Genetics), Protein-Binding

First Page

4438

Last Page

4445

JAX Source

J Immunol 2001 Apr; 166(7):4438-45.

Abstract

Histocompatibility (H) Ags are responsible for chronic graft rejection and graft vs host disease in solid tissue and bone marrow transplantation among MHC-matched individuals. Here we defined the molecular basis of self-nonself discrimination for the murine chromosome 7 encoded H47 histocompatibility locus, known by its trait of graft-rejection for over 40 years. H47 encodes a novel, highly conserved cell surface protein containing the SCILLYIVI (SII9) nonapeptide in its transmembrane region. The p7 isoleucine-to-phenylalanine substitution in SII9 defined the antigenic polymorphism and T cell specificity. Despite absence of the canonical consensus motif and weak binding to D(b) MHC I, both H47 peptides were presented to CTLs. However, unlike all the other known H loci, the relative immunogenicity of both H47 alleles varied dramatically and was profoundly influenced by neighboring H loci. The results provide insights into the peptide universe that defines nonself and the basis of histoincompatibility.

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