title: Helper T cell recognition of the variable domains of a mouse myeloma protein (315). Effect of the major histocompatibility complex and domain conformation.
abstract: We have examined the recognition of the variable (V) domain of the heavy (VH) and light (V lambda 2) chains of mouse myeloma protein 315 by helper T cells. 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 three 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. The data indicate that there exists helper T cells which recognize each member of the M315 pair of V domains independent of the other, and that these V domains are recognized like conventional extrinsic protein antigens.
mesh_terms: D000818:Animals; D001666:Binding Sites, Antibody / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology*; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009194:Myeloma Proteins / Q000235:genetics / Q000276:immunology*; D011487:Protein Conformation; D011995:Recombination, Genetic; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D002352:Carrier Proteins; D006183:H-2 Antigens; D007135:Immunoglobulin Variable Region; D009194:Myeloma Proteins