Structural analyses define an additional H-2D region class I antigen that is expressed by a variant mouse strain

Area of Science:

• Immunogenetics
• Molecular immunology
• MHC complex genetics

Background:

• The H-2D region of the mouse major histocompatibility complex (MHC) exhibits genetic complexity due to variations in gene and product numbers across different haplotypes.
• Understanding the genetic basis of these disparities is crucial for comprehending immune system diversity and function.

Purpose of the Study:

• To investigate the genetic basis of H-2D region complexity by comparing antigens expressed by two mouse strains, STU and B10.SAA48, both known to express Dw3 antigens.
• To characterize the relationship between Dw3 and other D region antigens, including a newly identified antigen, Lw3.

Main Methods:

• Comparative serologic analysis using monoclonal antibodies.
• Fluorometric assays to quantify antigen expression.
• Peptide mapping to determine molecular structure and identify similarities/differences between antigen products.
• Genetic mapping to localize the gene encoding the Lw3 antigen.

Main Results:

• Both STU and B10.SAA48 mouse strains express indistinguishable Dw3 molecules.
• B10.SAA48 mice uniquely express an additional antigen, Lw3, with evidence suggesting its gene maps to the D region.
• Peptide mapping indicated Dw3 and Lw3 are products of separate genes but are more homologous to each other than to Dd and Ld molecules.
• Dw3 and Lw3 molecules showed unexpected homology to Ddx and Dw25 molecules, defining a distinct 'Dw3-family' of related antigens, separate from the 'Ld-family'.

Conclusions:

• The findings suggest the existence of separate genes for Dw3 and Lw3 antigens within the H-2D region.
• The identification of the Dw3-family, distinct from the Ld-family, highlights novel structural relationships among D region antigens.
• These results provide evidence for intra-D region recombination or mutation as mechanisms contributing to the genetic complexity of the H-2D region.