The COI mitochondrial gene encodes a minor histocompatibility antigen presented by H2-M3.
We found that (LP x C57BL/6)F1 mice could raise a CTL response against parental C57BL/6 cells. These CTLs recognized a maternally transmitted, H2-M3wt-restricted, minor histocompatibility Ag (MiHA) that is widely distributed among many strains of mice and encoded by the COI mitochondrial gene. The wild-type MiHA is the COI N-terminal hexapeptide. Sequencing the 5' end of the COI gene in LP and C57BL/6 mice showed that the LP allele arose by a T-->C transition in the third codon, which caused substitution of threonine for isoleucine. Molecular characterization of this MiHA and the demonstration that it is presented exclusively by H2-M3: 1) support the concept that differential expression of MiHA in MHC-identical animals is caused by polymorphism of the MiHA gene proper; 2) expand our knowledge of the repertoire of self-peptides naturally presented by H2-M3 and show that this MHC class I molecule can present short endogenous peptide ligands; and 3) suggest that mitochondrial DNA mutations that modify the repertoire of H2-M3-associated mitochondrial peptides are representative of mitochondrial DNA mutations in general.
Morse
M C
MC
University of Montreal, Maisonneuve-Rosemont Hospital, Québec, Canada.
Bleau
G
G
Dabhi
V M
VM
Hétu
F
F
Drobetsky
E A
EA
Lindahl
K F
KF
Perreault
C
C
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics*; D001483:Base Sequence; D003433:Crosses, Genetic; D004272:DNA, Mitochondrial / Q000276:immunology*; D003576:Electron Transport Complex IV / Q000235:genetics* / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000276:immunology*; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008814:Mice, Inbred NZB; D015778:Minor Histocompatibility Antigens / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D011247:Pregnancy; D013329:Structure-Activity Relationship
D004272:DNA, Mitochondrial; D006183:H-2 Antigens; D015778:Minor Histocompatibility Antigens; D003576:Electron Transport Complex IV