T helper cell recognition of idiotopes on lambda 2 light chains of M315 and T952: evidence for dependence on somatic mutations in the third hypervariable region.

Previous work has indicated that BALB/c T helper cells (Th) recognize an idiotope expressed on a 88-114/117 fragment of V lambda 2 of BALB/c myeloma protein 315. In the present study the antigenic structure of this idiotope was further analyzed. Conventional carrier-specific Th elicited by immunization of BALB/c mice with free lambda 2(315) did not cross-react with the free lambda 2 chain of the BALB/c myeloma protein T952 which differs from lambda 2(315) in five amino acid positions (38, 94, 95, 96, 99). Similarly, Th primed with free lambda 2T952 did not respond to a boost with free lambda 2(315). Thus, BALB/c lambda 2(315)-specific Th recognize an idiotope that depends on some or all of the residues at positions 94, 95, 96 and 99. Furthermore, free lambda 2T952 contains an idiotope immunogenic to Th that depends on some or all of residues 38, 94, 95, 96 and 99. Th recognition of the free lambda 2T952 idiotope was quenched upon H + L chain assembly because Th elicited by free lambda 2T952 did not respond to a boost with the complete T952 myeloma protein. In contrast to the lack of Th cell cross-reactivity, some of the antisera from BALB/c mice immunized with free lambda 2T952 cross-reacted with free lambda 2(315), free lambda lJ558 and free lambda 3CBPC49 but not with free kappa W3129 or polyclonal L chains. The H chain of T952 (alpha, kappa 2) myeloma protein was abnormally short (Mr = 48 000) and T952 existed as a halfmere probably due to this H chain deletion. Furthermore, H and L chains were disulfide bonded to each other.