Genetic control of the immune response to staphylococcal nuclease. III. Time-course and correlation between the response to native nuclease and the response to its polypeptide fragments.

Abstract

The progression of the Ir gene-controlled antibody response to staphylococcal nuclease in mice with repeated immunizations was examined. H-2-linked control of the response to a single immunization with 100 .mu.g of nuclease in complete Freund''s adjuvant was confirmed. Among strains of the high responder H-2" haplotype, the response of the A/J mice was about 10-fold higher than that of the B10.A, indicating additional non-H-2-linked control. The low responder C57BL/10 (H-2b) strain produced antibody levels as high as or higher than those of the congenic high responder B10.A (H-2") strain when both strains were repeatedly immunized, indicating complexity even in the H-2-linked control of the response to this small monomeric protein. Polypeptide fragments of nuclease were studied as immunogens. The antibody response to 1 fragment (residues 99-149) followed the same pattern among 5 strains tested as that to whole nuclease. In this case the C57BL/10 was found to be a nonresponder rather than a low responder, failing to develop a response despite repeated immunizations. The C57BL/10 showed a low but significant response to another fragment (residues 1-126) of nuclease. The apparent H-2-linked control of the response to whole nuclease is a reflection of the ability to recognize a determinant(s) in the region from residues 99-149, and that the eventual response of the C57BL/10 strain after hyperimmunization reflects the recognition of other determinants. If these observations reflect the common recognition of a determinant on native nuclease and on a random-conformation fragment, they have implications about the conformational specificity of the receptors, or the flexibility of the determinants, involved in H-2-linked Ir-gene control. Evidence is presented for a possible 2nd H-2-linked gene (or genes) controlling the response to other determinants of nuclease expressed on the polypeptide fragments.