Rich, Susan Solliday

Abstract MLR suppressor factor (MLR-SF) optimally suppresses MLR responses only of responder cells which are compatible in the I-C subregion with cells producing the factor. Therefore, presence of MHC-encoded determinants on MLR-SF has been investigated, with particular interest in I-C, as well as the possible role of I-J determinants. Suppressor activity of supernates of alloantigen-activated spleen cells was tested after passage over solid immunoadsorbants prepared with various anti-H-2 subregion sera. Immunoadsorbants with specificity towards K and D region products were ineffective while several preparations with I region specificity removed suppressor activity from factors of the appropriate haplotype. The single subregion specificity common to all adsorbing preparations was I-C. Recently, ambiguity has developed with regard to genetic resolution of I-C and adjacent subregions, including difficulties of serologic differentiation of I-C products of the k and d haplotypes. Antisera prepared in I-Ck/I-Cd disparate strain combinations have identified T cell restricted determinants which are distinct between these haplotypes. MLR-SF prepared from (BALB × CBA)F1 were passed over I-Cd and I-Ck specific adsorbants and residual activity tested in MLR with each parental responder cell. Exposure to anti-I-Cd removed suppressor activity for the BALB response, leaving intact suppression of CBA responses. The reciprocal situation also obtained. Furthermore, acid elution of anti-I-Cd columns exposed to F1 factor yielded material which suppressed BALB but not CBA MLR. Antisera with anti-I-Jk specificity did not remove suppressor activity of various H-2k factors. In addition, control factors passed over anti-I-Jk columns did not acquire suppressive activity, indicating that leaching of small quantities of anti-I-J antibodies had not concealed actual binding of suppressor molecules, by inducing a distinct form of suppression. Thus, I-C subregion products, restricted to T lymphocyte expression, exhibit unique association with MLR-SF suppression of MHC stimulated immune responses.