Helper T cell recognition of the variable domains of a mouse myeloma protein (315). Effect of the major histocompatibility complex and domain conformation.

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Abstract
The recognition of the variable (V) domain of the H (VH) and L (V.lambda.2) chains of mouse myeloma protein 315 by helper T cells was examined. Mice were primed with the isolated V domain in complete Freund''s adjuvant, and carrier (V domain)-primed spleen cells were transferred together with hapten (NIP)-primed spleen cells to recipient mice that were boosted with NIP3-Fab-315. The helper cell response to both domains was governed by H-2-linked immune response (Ir) genes, and VH-315 and V.lambda.2 displayed different Ir phenotypes. H-2k conferred high responsiveness to VH on 3 different genetic backgrounds, BALB/c, C3H and B10; mice of the d and b haplotypes were low responders. Conversely, H-2d conferred high responsiveness to V.lambda.2 on two backgrounds, BALB/c and C3H, whereas mice of the k haplotype were low responders to this domain. Non-H-2 genes of the B10 background extinguished the helper cell response to V.lambda.2 in animals with the high responder d haplotype. The VH Ir gene mapped to the K-A interval of the H-2 complex. Unfolded (completely reduced and alkylated) V domains primed helper cells as efficiently as folded domains for responses to NIP3-Fab-315, indicating that the helper cells recognized an antigenic determinant that was not conformation-dependent. Helper T cells apparently exist which recognize each member of the M315 pair of V domains independent of the other. These V domains are recognized like conventional extrinsic protein antigens.