Recognition of lambda 1 and lambda 2 murine light chains by carrier-specific isologous T helper cells; effect of L-H chain assembly.

Previous studies from this laboratory have revealed an antigenic site located on the variable domain of the lambda 2 light chain of BALB/c myeloma protein 315 (the V lambda 2(315) site). This site is recognized by conventional carrier-specific T helper cells (Th) of BALB/c mice and is expressed on both the free and assembled V lambda 2(315) domain. The present work defines two new antigenic sites associated with murine lambda chains. The first site was associated with free lambda 1-chain of myeloma protein J558. It was recognized by splenic Th from animals that had been primed with free lambda 1J558 in complete Freund's adjuvant; when transferred to irradiated animals the primed Th responded to a boost with (4-hydroxy-5-iodo-3-nitro-phenyl)acetate (NIP)-free lambda 1J558 in saline, but did not respond to NIP-complete J558 or NIP-free lambda 2(315). Priming with complete J558 failed to elicit Th that responded to NIP-free lambda 1J558. This determinant was therefore only expressed on the free (as opposed to the assembled) form of lambda 1J558, and it was not shared with free lambda 2(315). The second antigenic site was shared between free lambda 1J558 and free lambda 2(315). It was defined by free lambda 2(315)-primed Th which responded to a boost with NIP-free lambda 1J558. Since priming with free lambda 1J558 did not elicit Th that recognized NIP-free lambda 2(315), the cross-reaction was undirectional. The free lambda 2(315)-primed Th failed to respond to the complete J558, and M315-primed Th failed to respond to NIP-free lambda 1J558, indicating that the second (cross-reactive) antigenic site, like the first, was only expressed on free lambda chains. Completely reduced and alkylated (unfolded) free lambda 1J558 and free lambda 2(315) chains elicited Th that recognized native (folded) free chains. Thus, free lambda 1J558 bears two antigenic determinants recognized by Th, one private and a second shared with free lambda 2(315). Lambda 2(315) also bears two determinants, a cross-reactive one on free lambda 2(315) shared with free lambda 1J558, and a private one located on the V lambda 2(315) domain of the complete M315. The discussion is focused on possible explanations for the quenching of the two new lambda chain determinants upon light-heavy chain assembly and why, by contrast, the private V lambda 2(315) site is maintained in the complete M315.