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Maternally transmitted antigen of mice: a model transplantation antigen
K Fischer Lindahl1, E Hermel, B E Loveland
1Howard Hughes Medical Institute, Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235-9050.
Abstract:
Molecular identification proved Mta, the maternally transmitted antigen of mice, to be a model minor histocompatibility (H) antigen. It consists of a peptide, MTF, that is presented on the cell surface by an H-2 class-I molecule, HMT. MTF is derived from ND1, a mitochondrially encoded protein, and the amino-terminal N-formyl-methionine is essential for binding to HMT; conservative substitutions at the sixth residue causes MTF to be a minor H antigen. HMT is encoded by the M3 gene at the telomeric end of the H-2 complex. The peptide-binding site of HMT is hydrophobic, and allelic forms of the mature protein differ by only three amino acids. Homologues and analogues of the mouse Mta system have recently been identified in rats.
Insights
The maternally transmitted antigen (Mta) in mice is a model minor histocompatibility (H) antigen. It involves a peptide (MTF) presented by an H-2 class-I molecule (HMT), crucial for understanding H antigen variations.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- The maternally transmitted antigen (Mta) in mice serves as a model for minor histocompatibility (H) antigens.
- Mta consists of a peptide (MTF) presented by an H-2 class-I molecule (HMT).
Purpose of the Study:
- To elucidate the molecular basis of the Mta minor histocompatibility antigen system.
- To investigate the structural and genetic characteristics of HMT and its interaction with MTF.
Main Methods:
- Molecular identification and characterization of Mta components.
- Analysis of peptide-MHC interactions and genetic mapping of the HMT gene.
Main Results:
- Mta is a minor H antigen comprising the MTF peptide derived from the mitochondrially encoded ND1 protein.
- The N-formyl-methionine of MTF is critical for binding to the HMT molecule, encoded by the M3 gene.
- Allelic variations in HMT involve three amino acids, affecting its hydrophobic peptide-binding site.
Conclusions:
- The Mta system provides a well-defined model for studying minor H antigen presentation and recognition.
- Understanding the Mta system contributes to knowledge of immune responses and transplantation tolerance.
- Homologues of the mouse Mta system have been identified in rats, suggesting conserved mechanisms.