Fine specificity of the H-2 linked immune response gene for the gallinaceous lysozymes

An immune response (Ir) gene is described which controls the ability of mice to respond to seven very closely related gallinaceous egg white lysozymes (GEL). This Ir-GEL gene locus is linked to the major histocompatibility locus of the mouse and operates at the level of the T cell. Responsiveness to the nonimmunogenic prototype hen egg white lysozyme (HEL) is dominant and is unrelated to age or sex of the animals, or to dose of protein administered. Ninety percent of C57BL/6 mice are absolute nonresponders to the nonimmunogenic lysozymes in complete Freund's adjuvant. The remaining mice exhibit severely restricted responses, with different anti-HEL clonotypes appearing in individual mice. The fine specificity of the Ir-GEL locus is evident in the discrimination of as few as two amino acid differences in a single region of the lysozyme molecule. This very precise distinction determines whether there will, or will not, be any response to the multideterminant molecule.