TY - JOUR
T1 - Distinguishing self from nonself
T2 - Immunogenicity of the murine H47 locus is determined by a single amino acid substitution in an unusual peptide
AU - Mendoza, L. M.
AU - Villaflor, G.
AU - Eden, P.
AU - Roopenian, D.
AU - Shastri, N.
PY - 2001/4/1
Y1 - 2001/4/1
N2 - 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 Db 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.
AB - 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 Db 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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U2 - 10.4049/jimmunol.166.7.4438
DO - 10.4049/jimmunol.166.7.4438
M3 - Article
C2 - 11254699
AN - SCOPUS:0035313640
SN - 0022-1767
VL - 166
SP - 4438
EP - 4445
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -