Cross-reactive idiotypes of monoclonal anti-Iak antibodies: characterization with xenogeneic anti-idiotypic reagents and expression in anti- H-2 humoral responses.

Abstract

Heterologous anti-idiotypic reagents were used to examine the idiotypic repertoire of l-Ek- or l-Ak-specific monoclonal antibodies (mAbs) directed at la.7- or la.1-associated determinants, respectively. A rabbit anti-idiotypic antiserum to the A.TH anti-la.7 mAb 41.A was shown to recognize, in direct idiotype binding and competitive inhibition of heterologous idiotype binding assays: i) individual idiotypic specificities (Idl) of mAb 41.A; ii) identical or similar cross-reactive idiotypic specificities (IdX) expressed on ten anti-la.7 mAbs (i.e., A.TH mAbs 10.A, 10.B, 40.C, 40.H, and 41.A, C3H.SW mAb 14-4-4S, and A.BY mAbs 81.A, 81.C, 81.H, and 81.N), all of which defined determinants in the same steric domain of the I-Ek molecule (cluster I); and iii) another set of recurrent idiotypic specificities expressed on two A.TH mAbs (39.I and 39.J) defining polymorphic determinants of the l-Ek and l-Ak molecules, respectively. Reciprocally, in direct idiotype binding or inhibition of cellular mAb binding assays, pig and rabbit anti-idiotypic antibodies to the C3H.SW mAb 14-4-4S recognized IdX on A.TH anti-la.7 mAbs defining cluster I but not on other anti-l-Ek mAbs directed at determinants spatially distant from that domain. Similar studies revealed that a rabbit anti-idiotypic antiserum to the A.TH anti-la.1 mAb 40.M recognized Idl on its homologous ligand and several sets of IdX, one of which was found expressed on five A.TH mAbs (i.e., 40.M, 40.N, 39.B, 40.A, and 39.E) defining la.1-associated determinants clustered into the same polymorphic region of the l-Ak molecule. Like the 14-4-4S idiotype, which was previously shown to be present in C3H.SW anti-C3H humoral immune responses, some A.TH anti-lak mAb idiotypes (such as mAb 40.B, an l-Ak-, l-Ek-specific mAb) were found expressed in A.TH anti-A.TL antisera. Anti-la.7 or -la.1-associated IdXs were detectable, although at variable levels, in anti-A.TL antisera raised in A.TH, A.BY, BALB/b, or B10.S(7R) strains.These data provide evidence that lak-specific mAbs represent families of B cell clone products sharing idiotypic markers, that such markers may be shared between strains with different Igh-C genes, and that in most cases, idiotypic sharing correlates with specificity for the same epitope region on the antigen.