Dependence of immune responses of “nonresponder” H-2s mice on determinant concentration in poly(GLU60 ALA30 TYR10) and on complementation between nonresponder mice of the same H-2p haplotype

Abstract

It has been conclusively shown that there are conditions under which mice of H-2^s halotype, previously considered to be nonresponders to the random terpolymer (Glu⁶⁰Ala³⁰Tyr¹⁰)_n, do respond. These T cell dependent responses are associated with all GAT¹⁰ preparations which consist of a mixture of heterogeneous polymers containing varying amounts of the three amino acids and especially tyrosine. Moreover as the above mice respond to the closely related polymers GA, GAL¹⁰ and GAT⁴ but not to GT which is immunosuppressive, GAT¹⁰ can be considered to consist of immunogenic and nonimmunogenic (tolerogenic) molecules, the latter associated with GAT containing glutamyl determinants with high concentrations of tyrosine. It is therefore, suggested that the Ir gene controlling the positive responses against the GAT¹⁰ polymers recognize GA determinants (Ir GA gene). For H-2^s mice immunized with 10 μg the entire GAT¹⁰ preparation is non-immunogenic. However, immunization with 100 μg (in complete Freund's adjuvant) activates both helper and suppressor T cells. Between days 14–21, the balance between these two distinct classes of T cells is in favour of the helper T cells which then results in antibody production. The injections of anti-l-J^s antiserum into SJL mice immunized with 10 μg GAT¹⁰ has accomplished the same effect by elimination of the suppressor T cells (Pierreset al., 1978). These findings indicate that in most immune responses, we are dealing with balances between helper and suppressor T cells rather than absolutes. An unusual ‘complementation’ in responses by F1 mice of H-2^p haplotype has been presented. Although none of the inbred or cogenic strains of mice of H-2^p haplotype respond to GAT¹⁰, of several F1 combinations studied only (B10.P × P) F1 mice have responded to 10–100 μg GAT¹⁰. The nonresponsiveness of P/J mice to MBSA-GAT¹⁰ indicates a possible deficiency in these mice at the B cell level. This, coupled with the responses of the F1 hybrids of two nonresponding parents suggest that we might be dealing with a mechanism of complementation of two nonresponders analogous to that reported on by Munro and Taussig, i.e. complementation of two sites of nonresponsiveness. One site might be a defect in the making of helper factor, which is a T cell defect, and the other might be a defect in the response to helper factor i.e. a B cell defect.