A new H-2-linked class I gene whose expression depends on a maternally inherited factor

Area of Science:

• Immunology
• Genetics
• Cell Biology

Background:

• Maternally transmitted antigen (Mta) is a medial histocompatibility antigen recognized by cytotoxic T lymphocytes.
• Unlike major H antigens, Mta is a weak transplantation antigen and does not restrict T-cell recognition of minor H antigens.
• Medial H antigens are typically encoded by genes near the H-2 complex, but Mta exhibits extrachromosomal maternal inheritance.

Purpose of the Study:

• To investigate the inheritance pattern and genetic basis of Mta expression.
• To determine the factors responsible for Mta negativity in certain mouse substrains.
• To elucidate the interaction between cytoplasmic and chromosomal factors in Mta expression.

Main Methods:

• Analysis of Mta expression in different mouse strains and substrains.
• Embryo transfer and foster nursing experiments to assess maternal influence.
• Backcrossing experiments to study the role of chromosomal genes and cytoplasmic factors.
• Genetic linkage analysis to identify genes involved in Mta expression.

Main Results:

• Mta expression follows maternal inheritance, determined by a cytoplasmic factor (Mtf) transmitted through the egg.
• Specific substrains (NZB, NZO, NMRI) are Mta-negative due to their cytoplasmic genes.
• Expression of Mta2 is possible in Mta-negative strains when combined with appropriate cytoplasmic factors.
• A gene, Hmt, located near the H-2 complex, is required for Mta expression, in addition to the cytoplasmic factor.

Conclusions:

• Mta expression is controlled by a dual genetic system involving a maternally inherited cytoplasmic factor (Mtf) and a chromosomal gene (Hmt) linked to the H-2 complex.
• This finding challenges the typical understanding of histocompatibility antigen inheritance.
• The interplay between cytoplasmic and nuclear genes is crucial for the regulation of Mta expression.