The T lymphocyte response to syngeneic λ2 light chain idiotopes. Significance of individual amino acids revealed by variant λ2 chains and idiotope‐mimicking chemically synthesized peptides

Abstract

In the present study we have investigated the structure of the helper T cell (Th)-defined idiotope (Id) of myeloma protein 315 lambda 2 light chain (lambda 2(315] in BALB/c (H-2d) mice which carry a high-responder immune response gene for this Id. Three peptides were synthesized which spanned the third hypervariable region (HV3) of lambda 2(315): peptides 88-99, 94-108 and 91-108. Only peptide 91-108 was capable of eliciting carrier-specific Th that recognized M315 or free lambda 2(315). These Th did not recognize lambda 2(5-7) chain which differs from lambda 2(315) at 4 positions in this region; these are Tyr94, Ser95, Thr96, Tyr98 for lambda 2(5-7) and Phe94, Arg95, Asn96, Phe98 for lambda 2(315). Immunization with peptide analogues revealed that substitution of Tyr for Phe94 was compatible with Id-lambda 2(315) mimicry, but substitution of Ser for Arg95 or Thr for Asn96 destroyed the Th-recognized Id. Furthermore, Th primed with lambda 2(5-7) chain did not cross-react with lambda 2T952; these lambda 2 chains only differ from each other at positions 98 and 99 at the V lambda 2-J lambda 2 junction. The data indicate that individual amino acids of short peptide segments are critical for Th-recognized Id of the lambda 2 HV3 loop and V lambda 2-J lambda 2 junction. Furthermore, the immunogenicity of a small peptide suggests that the carrier (lambda 2)-specific Th recognize Id that have been processed by antigen-presenting cells (APC). This implies the existence of two categories of "internal images" of foreign or of self antigens: (a) serologically defined and (b) T lymphocyte defined. We propose that as a rule, Id processing by APC, including B cells, destroys the first and reveals the second category. The possible physiological function of these Id-specific T cells in network interactions with B cells is discussed.