H-2 Antigens pp 315-320 | Cite as

Mutation in the Aβ Gene of B6.C-H-2bm12. Antibody Binding Site VS. T Cell Recognition Sites

  • Kathleen A. Donovan
  • Sujay K. Singh
  • Chella S. David
Part of the NATO ASI Series book series (NSSA, volume 144)


Four functional Ia genes are coded within the I (immune response) region of mouse, e.g., Aα, Aβ, Eα, and Eβ (Jones et al. 1978; Klein et al. 1981). In recent years using congenic inbred and recombinant strains of mice, several investigators have demonstrated a relationship between Ia molecules and immune response. The I-A mutant mouse strain, B6.C-H-2bm12 is to date the only known example of a mutant involving the class II genes. This strain was originally identified by Melvold and Kohn from a (B6 × BALB/c)F1 by reciprocal skin graft rejection. The findings on this mutant, B6.H-2bm12, have helped in further characterization of fine specificities on an Ia molecule. In analyzing this mutant strain, McKenzie and co-workers were able to map the mutation to the I-A subregion using complementation studies with recombinant strains. Tryptic peptide maps revealed a limited number of differences between 86 and bm12, mapping the mutation to the I-A beta polypeptide chain (McKean et al. 1981). The tryptic peptide studies showed that this mutation is not due to a single point mutation, but involves a minimum of three different amino acid substitutions. Recently, McIntyre and Seidman (1984) have cloned and sequenced a gene coding for the bm12 A-beta polypeptide chain. Three nucleotide substitutions result in three amino acid substitutions within a span of five amino acids; isoleucine at position 67, arginine at position 70 and threonine at position 71, are being substituted by phenylalanine, glutamine and lysine respectively (Fig. 1). Two of these amino acid substitutions (arginine-glutamine and threonine-lysine) are non-conservative changes in the tertiary structure of the beta polypeptide chain, resulting in the observed alterations in the serology and function of the bm12 I-A molecule. Amino acid sequence comparison also shows that two of the amino acid substitutions found in the bm12 A8 chain are found at the same positions in several human class II beta chains (McIntyre and Seidman, 1984). These comparisons suggest that the bm12 mutation in the I-A beta gene arose from a gene-conversion type event in which another class II beta chain gene acted as a donor sequence.


Amino Acid Substitution Linear Determinant Gene Conversion Event Functional Determinant Antibody Binding Site 
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Copyright information

© Springer Science+Business Media New York 1987

Authors and Affiliations

  • Kathleen A. Donovan
    • 1
  • Sujay K. Singh
    • 1
  • Chella S. David
    • 1
  1. 1.Department of ImmunologyMayo Clinic and Medical SchoolRochesterUSA

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